专家信息:
巩长旸,男,1980年9月出生,博士学位。四川大学华西医院生物治疗全国重点实验室、“2011计划”生物治疗协同创新中心、生物治疗转化医学国家重大科技基础设施、国家“重大新药创制”科技重大专项“国家创新药物研发综合大平台”学术带头人,研究员,博士研究生导师。2018年国家自然科学基金优秀青年基金获得者,入选2015年国家中组部“万人计划”青年拔尖人才支持计划,获2013年全国百篇优秀博士学位论文提名奖,2013年四川省百篇优秀博士学位论文,中国抗癌协会青年理事会理事,中国生物医学工程学会纳米医学与工程学分会常务委员,中国抗癌协会纳米肿瘤学分会委员,中国生物物理协会纳米生物学分会委员会委员,中国生物材料学会纳米生物材料分会第二届委员会委员,中国病理生理学会免疫学专业委员会委员,中国生物物理协会材料生物学与智能诊疗技术分会委员,中国医药生物技术协会生物医学成像技术分会第一届委员会委员,四川省药学会纳米药物专业委员会委员,第十三批四川省学术和技术带头人,第十三批四川省卫生健康委员会学术技术带头人,获2021年四川省杰出青年科技人才项目。1999-2003年就读于四川大学生物工程专业,获理学学士学位。2005年在四川大学生物治疗国家重点实验室攻读博士学位(硕博连读),在著名肿瘤治疗学家魏于全院士的指导下完成博士论文研究工作。2010年获四川大学细胞生物学专业博士学位,同年7月起任四川大学华西医院生物治疗国家重点实验室助理研究员、副研究员、研究员。主要研究领域为新型自组装基因、疫苗和药物递送系统、医用生物材料、纳米生物技术、肿瘤治疗。主持和参与国家自然科学基金优秀青年基金、面上项目、青年基金,科技部863重点项目“纳米生物材料研发”,科技部重点研发计划,科技部“重大新药创制”科技重大专项,教育部博士点基金,四川省科技支撑计划等多项国家及省部级基金项目。以第一发明人申报中国发明专利13项,其中13项已授权。现已发表SCI学术论文100余篇(所有工作均在国内完成),论文被引用XXX次,他引XXX次,h-index为33。其中,以通讯或第一作者在Nat Commun (IF 17.694), J Am Chem Soc (IF 16.383), Adv Mater (IF 32.086), Adv Funct Mater (IF 19.924), ACS Nano (IF 18.027), Adv Drug Deliver Rev (IF 17.873), Adv Sci (IF 17.521), Chem Eng J (IF 16.744), Biomaterials (IF 15.304), Small (IF 15.153), Small Methods (IF 15.153), Acta Pharm Sin B (IF 14.903), Nano Lett (IF 12.262)等国际杂志发表SCI论文100余篇(IF>10论文34篇,10>IF>5论文28篇),被Nat Rev Cancer, Nat Mater, Nat Biotechnol, Nat Commun, Chem Rev, Chem Soc Rev, Prog Polym Sci, Adv Drug Deliver Rev, Adv Mater, ACS Nano, Adv Funct Mater等国际SCI学术期刊引用XXX次,他引XXX次。三篇论文(ACS Nano, 2017; Biomaterials, 2013; Int J Pharm, 2009)入选ESI“高被引用论文”。研究成果已经作为他人进一步研究的基础, 并得到其他研究论文的证实。受Adv Drug Deliver Rev (IF 17.873), Nano Res (IF 10.262)等期刊邀请撰写特邀综述6篇。并受美国Nova出版社之邀,参与编写英文书 “Polymer Aging, Stabilizers and Amphiphilic Block Copolymers”. Editors: Liudvikas Segewicz and Marijus Petrowsky. Nova Publishers. 2011-1st Quarter.(ISBN: 978-1-60692-928-5)。由于相关领域研究工作受到国际重视,受主编之邀,任Chinese Chem Lett (IF 8.455), BioMed Res Int (IF 3.246)等学术期刊编委。为Nat Commun, Adv Mater, Adv Funct Mater, Adv Sci, J Am Chem Soc, ACS Nano, Chem Eng J, Biomaterials, Small, Small Method, Nano Lett等50余种国际期刊审特邀稿人。
教育及工作经历:
2003年毕业于四川大学,获学士学位。
2010年于四川大学获博士学位。
2010年起在四川大学华西医院生物治疗国家重点实验室进行科研工作。
学术兼职:
1. 任职名称:中国抗癌协会;职务:青年理事会理事;首任时间:2019年2月15日;届数:第一届,第二届;任期年限:2019年2月15日至2027年7月14日。
2. 任职名称:中国生物医学工程学会纳米医学与工程学分会;职务:常务委员;首任时间:2023年5月20日;届数:第二届;任期年限:2023年5月至2027年5月。
3. 任职名称:中国生物材料学会纳米生物材料分会;职务:委员会委员;首任时间:2019年10月;届数:第二届、第三届;任期年限:2019年10月至2027年10月。
4. 任职名称:中国生物物理协会纳米生物学分会;职务:委员会委员;首任时间:2021年8月;届数:第五届;任期年限:2021年8月至2025年8月。
5. 任职名称:中国抗癌协会纳米肿瘤学分会;职务:委员会委员;首任时间:2021年10月;届数:第三届;任期年限:2021年10月至2025年10月。
6. 任职名称:中国病理生理学会免疫学专业委员会;职务:委员;首任时间:2018年11月15日;届数:第八届、第九届;任期年限:2018年11月15日至今(第九届是2020年开始,好像六年一届)。
7. 任职名称:中国生物物理学会材料生物学与智能诊疗技术分会;职务:委员;首任时间:2021年8月;届数:第X届;任期年限:2021年8月至2025年8月。
8. 任职名称:中国医药生物技术协会生物医学成像技术分会;职务:委员会委员;首任时间:2019年10月;届数:第一届、第二届;任期年限:2023年11月至2027年10月。
9. 任职名称:中国生物医学工程学会纳米医学与工程学分会;职务:青年委员会委员;首任时间:2019年4月20日;届数:第二届;任期年限:2019年4月20日至2023年4月19日。
10. 任职名称:中国生物物理协会纳米生物学分会;职务:青年委员会委员;首任时间:2019年4月;届数:第五届;任期年限:2019年4月至2021年8月。
11. 任职名称:中国抗癌协会纳米肿瘤学分会;职务:青年委员会委员;首任时间:2018年8月6日;届数:第一届;任期年限:2018年8月6日至2022年8月5日。
12. 任职名称:四川省药学会纳米药物专委会;职务:委员;首任时间:2023年4月;届数:第一届;任期年限:2023年4月至2026年12月。
13. 任职名称:四川大学华西第二医院妇幼药物研究与转化实验室学术委员会;职务:委员;首任时间:2023年9月;届数:第一届;任期年限:2023年9月至2026年12月。
期刊任职:
1. 任职名称:Acta Pharmaceutica Sinica B(SCI,IF 14.5);职务:青年编委;首任时间:2023年9月;届数:第三届;任期年限:2023年9月至今。
2. 任职名称:Chinese Chemical Letters(SCI,IF 9.1);职务:青年编委;首任时间:2018年5月;届数:第二届、第三届,第四届;任期年限:2018年5月至2022年6月。
3. 任职名称:BioMed Research International(SCI,IF 2.276);职务:编委;首任时间:2013年3月;届数:第一届;任期年限:2013年3月至今。
4. 任职名称:International Scholarly Research Notices;职务:编委;任期年限:2014年5月至2017年7月。
5. 任职名称:Advances in Pharmaceutics;职务:编委;任期年限:2013年5月至2016年8月。
6. 任职名称:药学学报;职务:青年编委;首任时间:2023年9月;届数:第三届;任期年限:2023年9月至2022年6月。
7. 任职名称:四川大学学报(医学版);职务:青年编委;首任时间:2023年3月;届数:第六届;任期年限:2023年5月至2025年4月。
主讲课程:
资料更新中……
培养研究生情况:
资料更新中……
招生情况:
欢迎药学、生命科学、基础及临床医学、化学或其他相关专业背景的同学报考,乐意接受推免生。
研究方向:
1. 新型靶向基因传递系统。
2. 新型靶向药物传递系统。
3. 多糖类药物。
4. 细胞表面功能化修饰。
5. 医用高分子材料等研究工作。
承担科研项目情况:
负责和参与多项国家和省部级科研项目,包括国家科技部863项目,“重大新药创制”国家重大专项,国家自然科学基金,四川省科技支撑计划,教育部博士点基金,四川大学优秀青年学者基金等。
2011年1月,科技部“重大新药创制”科技重大专项,“新型多烯紫杉醇水性制剂研发”第一主研人员。
科研成果:
1. 发现PEG/PCL胶束是一种较理想的纳米药物传递系统,并以此为“跳板”做了一系列出击。针对临床紫杉醇注射液中聚氧乙烯蓖麻油易引起过敏反应的问题,他采用PEG/PCL纳米胶束包载紫杉醇和多烯紫杉醇,获得了可静脉注射的新型紫杉烷纳米缓释制剂显著提高其抗肿瘤效果并降低毒副作用,为创制新型紫杉烷水基制剂提供了新选择。
2. 姜黄素也具有疏水性,先是通过PEG/PCL纳米胶束单独包载姜黄素,制备出一种新型姜黄素纳米缓释制剂,为肿瘤转移的治疗提供了新思路,又开始考虑把姜黄素与其他药物作为一个共同体包载在PEG/PCL纳米胶束中。比如,与亲水性的阿霉素一起,可以在亲—疏水药物之间产生协同作用,显著提高肿瘤细胞对阿霉素的摄取;而与紫杉醇结合,可以在体内外显著提高紫杉醇的抗肿瘤效果,摒除紫杉醇耐药性的缺点。美国堪萨斯大学医学院分子生物学研究院副院长Shrikant Anant教授在Mol Cancer Ther上公开表示,巩长旸的方法“不使用有毒有机溶剂和剧烈条件,是高效、稳定、安全的”。
3. 温敏型水凝胶制备出来之后,巩长旸利用其包载紫杉醇、5-Fu等抗肿瘤药物,获得了可腹腔注射的新型原位缓释制剂,可显著提高腹腔化疗药物浓度和滞留时间,提高其抗肿瘤及抗腹腔转移效果;包载和厚朴酚,发现其对肺癌恶性胸腔积液有显著的治疗效果。其中,紫杉醇原位缓释凝胶制剂可以有效防治乳腺癌术后复发,载姜黄素温敏型水凝胶为解决大面积全皮缺损的修复奠定了基础。药物缓控释领域著名期刊J Control Release引用了巩长旸3篇关于温敏型水凝胶用于局部药物缓释的文章,并进行了正面评述:“水凝胶局部药物缓释体系减少了给药次数,有利于提高患者的依从性”。
4. 在研究中,发现温度敏感型水凝胶有良好的防治术后腹腔组织粘连的作用,并创新地提出了水凝胶防治腹腔粘连的作用机理。
发明公开:
[1]巩长旸, 梁秀琪, 吴秦洁. 一种智能响应型可注射水凝胶及其制备方法和应用[P]. 四川省: CN116763725A, 2023-09-19.
[2]巩长旸, 杨茜, 高玲, 郑岭楠, 魏院锋. 一种具有佐剂效应的水凝胶及其制备方法和用途[P]. 四川省: CN116688114A, 2023-09-05.
[3]巩长旸, 宋林江, 吴秦洁, 魏于全. 一种肿瘤靶向多功能非病毒基因载体及其制备方法和用途[P]. 四川省: CN113318242A, 2021-08-31.
[4]巩长旸, 吴秦洁, 王宁. 一种多功能外壳材料PMTPH及其制备方法和用途[P]. 四川省: CN112386711A, 2021-02-23.
[5]巩长旸, 吴秦洁, 王宁. 一种精氨酸修饰的聚乙烯亚胺及其制备方法和用途[P]. 四川省: CN112210077A, 2021-01-12.
[6]巩长旸, 罗晗, 杨茜, 朱精强, 李志辉, 唐怀荣. 一种包含胶束的可注射复合水凝胶双载药系统的制备方法[P]. 四川省: CN112156066A, 2021-01-01.
[7]巩长旸, 罗晗, 杨茜, 朱精强, 李志辉, 唐怀荣. 一种共载紫杉烷类胶束和铂类药物的可注射水凝胶及其制备方法和用途[P]. 四川省: CN112089729A, 2020-12-18.
[8]巩长旸, 吴秦洁, 王宁. 一种氨基酸修饰的聚乙烯亚胺化合物及其制备方法和用途[P]. 四川省: CN112094409A, 2020-12-18.
[9]巩长旸, 周长庚. 一种含硼纳米靶向药物的制备方法[P]. 四川省: CN111281975A, 2020-06-16.
[10]巩长旸, 吴秦洁, 何涛, 魏于全. 一种免疫佐剂及其制备方法[P]. 四川省: CN109694484A, 2019-04-30.
[11]巩长旸, 吴秦洁, 王宁. 寡聚透明质酸或其盐在制备治疗心肌梗死的药物中的用途[P]. 四川省: CN109528753A, 2019-03-29.
[12]蔡璐璐, 巩长旸, 童荣生, 王强, 余继英, 王岩. 一种抗癌天然产物藤黄酸的纳米制剂及其制备方法[P]. 四川: CN108619094A, 2018-10-09.
[13]巩长旸, 谢永美, 曾安琪, 杨超, 宋林江, 魏于全. 一种pH敏感型的SN#38胶束及其制备方法和用途[P]. 四川: CN106963731A, 2017-07-21.
[14]巩长旸, 吴秦洁, 宋林江, 魏于全. 一种用于基因传递的非病毒基因载体及其制备方法和用途[P]. 四川: CN106755027A, 2017-05-31.
[15]巩长旸, 吴秦浩, 魏于全, 李玲. 一种修饰的聚乙烯亚胺化合物及其制备方法和应用[P]. 四川: CN106188537A, 2016-12-07.
[16]巩长旸, 丁健, 刘新宇, 吴秦洁, 魏于全, 李玲. N,O-羧甲基化壳聚糖-多醛基透明质酸凝胶及其用途[P]. 四川: CN103897206A, 2014-07-02.
[17]钱志勇, 巩长旸, 魏于全, 赵霞. 包载化疗药物的聚合物水凝胶及其在预防肿瘤复发和防治术后腹腔粘连中的用途[P]. 四川: CN102973941A, 2013-03-20.
[18]钱志勇, 魏于全, 赵霞, 巩长旸. PCL-PEG-PCL三嵌段共聚物在制备医用防粘连材料中的用途[P]. 四川: CN101837006A, 2010-09-22.
发明授权:
[1]巩长旸, 梁秀琪, 吴秦洁. 一种智能响应型可注射水凝胶及其制备方法和应用[P]. 四川省: CN116763725B, 2023-11-24.
[2]巩长旸, 吴秦洁, 王宁. 一种氨基酸修饰的聚乙烯亚胺化合物及其制备方法和用途[P]. 四川省: CN112094409B, 2023-08-08.
[3]巩长旸, 吴秦洁, 王宁. 一种精氨酸修饰的聚乙烯亚胺及其制备方法和用途[P]. 四川省: CN112210077B, 2023-07-04.
[4]巩长旸, 宋林江, 吴秦洁, 魏于全. 一种肿瘤靶向多功能非病毒基因载体及其制备方法和用途[P]. 四川省: CN113318242B, 2023-03-10.
[5]巩长旸, 周长庚. 一种含硼纳米靶向药物的制备方法[P]. 四川省: CN111281975B, 2023-02-24.
[6]巩长旸, 罗晗, 杨茜, 朱精强, 李志辉, 唐怀蓉. 一种共载紫杉烷类胶束和铂类药物的可注射水凝胶及其制备方法和用途[P]. 四川省: CN112089729B, 2022-04-01.
[7]巩长旸, 吴秦洁, 王宁. 一种多功能外壳材料PMTPH及其制备方法和用途[P]. 四川省: CN112386711B, 2022-02-22.
[8]巩长旸, 吴秦洁, 何涛, 魏于全. 一种免疫佐剂及其制备方法[P]. 四川省: CN109694484B, 2021-08-27.
[9]巩长旸, 罗晗, 杨茜, 朱精强, 李志辉, 唐怀荣. 一种包含胶束的可注射复合水凝胶双载药系统的制备方法[P]. 四川省: CN112156066B, 2021-08-17.
[10]巩长旸, 吴秦洁, 王宁. 寡聚透明质酸或其盐在制备治疗心肌梗死的药物中的用途[P]. 四川省: CN109528753B, 2021-01-22.
[11]巩长旸, 吴秦洁, 宋林江, 魏于全, 姚少华. 一种用于基因传递的非病毒基因载体及其制备方法和用途[P]. 四川省: CN106755027B, 2021-01-15.
[12]巩长旸, 谢永美, 曾安琪, 杨超, 宋林江, 魏于全. 一种pH敏感型的SN-38胶束及其制备方法和用途[P]. 四川省: CN106963731B, 2020-08-21.
[13]巩长旸, 李玲, 吴秦洁, 魏于全. 一种修饰的聚乙烯亚胺化合物及其制备方法和应用[P]. 四川省: CN106188537B, 2018-07-13.
[14]巩长旸, 丁健, 刘新宇, 吴秦洁, 魏于全, 李玲. N,O-羧甲基化壳聚糖-多醛基透明质酸凝胶及其用途[P]. 四川省: CN103897206B, 2016-08-17.
[15]钱志勇, 魏于全, 赵霞, 巩长旸. PCL-PEG-PCL三嵌段共聚物在制备医用防粘连材料中的用途[P]. 四川省: CN101837006B, 2013-04-10.
实用新型:
[1]巩长旸, 周长庚. 一种含硼和含钆纳米药物的制备装置[P]. 四川省: CN212854063U, 2021-04-02.
现已在ACS Nano (12.033), Biomaterials (8.312), Nanoscale (6.739), J Biomed Nanotechnol (7.578), Nanomed-Nanotechnol (5.978), ACTA Biomater (5.684)等SCI学术期刊发表86篇,引用1500余次,他引1200余次,h-index为24。其中第一作者及通讯作者发表学术论文100余篇(IF>5论文25篇)。受J Biomed Nanotechnol (7.578), Curr Med Chem和Curr Drug Metab期刊邀请撰写特邀综述3篇。
参与编写英文专著:
[1]ChangYang Gong, Shuai Shi, PengWei Dong, MaLing Gou, XingYi Li, YuQuan Wei and ZhiYong Qian, A Novel Thermosensitive Composite Hydrogel Based on Poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PECE) Copolymer and Pluronic F127. Chapter 2 in the book of “Polymer Aging, Stabilizers and Amphiphilic Block Copolymers”. Editors: Liudvikas Segewicz and MarijusPetrowsky. Nova Publishers, USA. 2011-1st Quarter. (ISBN: 978-1-60692-928-5);
[2]XiaWei Wei, Gang Guo, ChangYang Gong, MaLing Gou, and Zhiyong Qian. Biodegradable polymers: Research and Applications. Chapter 12 in the book of “A Handbook of Applied Biopolymer Technology: Synthesis, Degradation and Applications”. Editors: Sanjay K Sharma and Ackmez Mudhoo. RSC Publisher, United Kingdom. 2011, 365-387. (ISBN: 978-1-60692-928-5)
代表性英文论文:( * 为通讯作者 )
[1]Shuang Ma, Yingjie Li, Furong Liu, Xinxin Wang, Zeyi Qin, Li Wang, Jin Yang, Li Wang, Wen Yang, Ning Wang, Yanjie You, Qinjie Wu, Changyang Gong*(Corresponding author) . Hierarchical-unlocking virus-esque NanoCRISPR precisely disrupts autocrine and paracrine pathway of VEGF for tumor inhibition and antiangiogenesis. Journal of Controlled Release.2024, 366, 505-518 SCI
[2]Yingjie Li, Shiyao Zhou, Qinjie Wu*, Changyang Gong*(Corresponding author).CRISPR/Cas gene editing and delivery systems for cancer therapy.Wiley Interdisciplinary Reviews-Nanomedicine and Nanobiotechnology.2024, 16(1): e1938 SCI
[3]Liping Bai#(co-first author), Jin Yang#(co-first author), Siting Yu, Zhongzheng Xiang, Yuanyuan Zeng, Meiling Shen, Xiaorong Kou, Qinjie Wu*, Changyang Gong*(Corresponding author) .Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses.Acta Pharmaceutica Sinica B.2024, 14(2): 821-835 SCI
[4]Wangxian Fu#(co-first author), Xinchao Li#(co-first author), Yingjie Li, Rui Luo, Chunqing Ou, Dongxue Huang, Xiuqi Liang, Yanjie You, Qinjie Wu*, Changyang Gong*(Corresponding author) .A programmable releasing versatile hydrogel platform boosts systemic immune responses via sculpting tumor immunogenicity and reversing tolerogenic dendritic cells.Biomaterials.2024, 305, 122444 SCI
[5]Shiyao Zhou, Yingjie Li, Qinjie Wu, Changyang Gong*(Corresponding author) .Nanotechnology-based CRISPR/Cas9 delivery system for genome editing in cancer treatment.MedComm-Biomaterials and Applications.2024, 3(1): e70 SCI
[6]Xinchao Li#(co-first author), Xiuqi Liang#(co-first author), Wangxian Fu, Rui Luo, Miaomiao Zhang, Xiaorong Kou, Yi Zhang, Yingjie Li, Dongxue Huang, Yanjie You, Qinjie Wu*, Changyang Gong*(Corresponding author) .Reversing cancer immunoediting phases with a tumor-activated and optically reinforced immunoscaffold. Bioactive Materials.2024, 35, 228-241 SCI
[7]Zichao Luo*, Duo Mao, Xinchao Li, Jing Luo, Changyang Gong*(Corresponding author), Xiaogang Liu*.Lanthanide-based nanoparticles for cancer phototherapy.Coordination Chemistry Reviews.2024, 508, 215773 SCI
[8]Xianzhou Huang, Tao He, Xiuqi Liang, Zhongzheng Xiang, Chao Liu, Shiyao Zhou, Rui Luo, Liping Bai, Xiaorong Kou, Xinchao Li, Rui Wu, Xinyu Gou, Xinyue Wu, Dongxue Huang, Wangxian Fu, Yingjie Li, Ruhan Chen, Ningyue Xu, Yixi Wang, Hao Le, Tao Chen, Yangsong Xu, Yuting Tang, Changyang Gong*(Corresponding author).Advances and applications of nanoparticles in cancer therapy.MedComm-Oncology .2024, 3: e67 SCI
[9]Ningyue Xu, Jun Wang, Lei Liu*, Changyang Gong*(Corresponding author).Injectable hydrogel-based drug delivery systems for enhancing the efficacy of radiation therapy: A review of recent advances. Chinese Chemical Letters.2024, 35(8): 109225 SCI
[10]Chunqing Ou#(co-first author), Meijia Xiao#(co-first author), Xinyue Zheng#(co-first author), Xianzhou Huang, Suleixin Yang, Yingying Leng, Xiaowei Liu, Xiuqi Liang, Linjiang Song, Yanjie You, Shaohua Yao*, Changyang Gong*(Corresponding author).Programmable double-unlock nanocomplex self-supplies phenylalanine ammonia-lyase for precise phenylalanine deprivation of tumors.Chinese Chemical Letters.2024, 35(8): 109275 SCI
[11]Xiuqi Liang, Xinchao Li, Rui Wu, Tao He, Furong Liu, Lu Li, Yi Zhang, Songlin Gong, Miaomiao Zhang, Xiaorong Kou, Tao Chen, Yanjie You, Meiling Shen, Qinjie Wu, Changyang Gong*(Corresponding author).Breaking the Tumor Chronic Inflammation Balance with a Programmable Release and Multi-stimulation Engineering Scaffold for Potent Immunotherapy. Advanced Science.2024, 11(28): 2401377 SCI
[12]Rui Luo, Hao Le, Qinjie Wu, Changyang Gong*(Corresponding author).Nanoplatform-Based In Vivo Gene Delivery Systems for Cancer Therapy.Small.2024, 20(30): 2312153 SCI
[13]Shunyao Zhu#(co-first author), Tao He#(co-first author), Yan Wang, Yushan Ma, Wenmei Li, Songlin Gong, Yanghui Zhu, Xiangwei Wang, Xu Xu, Qinjie Wu, Changyang Gong*(Corresponding author), Yanjie You*. A hierarchically acidity-unlocking nanoSTING stimulant enables cascaded STING activation for potent innate and adaptive antitumor immunity .Theranostics.2024, 14(15): 5984-5998 SCI
[14]Shiyao Zhou, Yingjie Li, Rui Wu, Tao Chen, Yangsong Xu, Hao Le, Yuting Tang, Qinjie Wu, Changyang Gong*(Corresponding author) .A Multifunctional Nutrient Transfer NanoCRISPR Scaffold Induces Metabolic Remodeling to Fuel Cancer Immunotherapy.Nano Today.2024, 58: 102451 SCI
[15]Ning Wang#(co-first author), Chao Liu#(co-first author), Yingjie Li, Dongxue Huang, Xinyue Wu, Xiaorong Kou, Xiye Wang, Qinjie Wu*, Changyang Gong*(Corresponding author). A cooperative Nano-CRISPR scaffold potentiates immunotherapy via activation of tumour-intrinsic Pyroptosis.Nature Communications.2023, 14: 779 SCI
[16]Tao He, Mingxing Hu, Shunyao Zhu, Meiling Shen, Xiaorong Kou, Xiuqi Liang, Lu Li, Xinchao Li, Miaomiao Zhang, Qinjie Wu*, Changyang Gong*(Corresponding author). A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence.Acta Pharmaceutica Sinica B.2023, 13(2): 804-818 SCI
[17]Li Wang#(co-first author), Chao Liu#(co-first author), Xinxin Wang, Shuang Ma, Furong Liu, Yi Zhang, Yan Wang, Meiling Shen, Xinyue Wu, Qinjie Wu*, Changyang Gong*(Corresponding author). Tumor-Specific Activated Nano-Domino-CRISPR to Amplify Intrinsic Oxidative and Activate Endogenous Apoptosis for Spatiotemporally Specific Therapy .Biomaterials.2023, 295, 122056 SCI
[18]Xiaowei Liu#(co-first author), Suleixin Yang#(co-first author), Li Wang#(co-first author), Xinyue Wu, Xinxin Wang, Chunqing Ou, Jin Yang, Linjiang Song, Shiyao Zhou, Qinjie Wu*, Changyang Gong*(Corresponding author).Hierarchically tumor-activated nanoCRISPR-Cas13a facilitates efficient microRNA disruption for multi-pathway-mediated tumor suppression.Theranostics.2023, 13(9): 2774-2786 SCI
[19]Linjiang Song#(co-first author), Jin Yang#(co-first author), Zeyi Qin#(co-first author), Chunqing Ou, Rui Luo, Wen Yang, Li Wang, Ning Wang, Shuang Ma, Qinjie Wu*, Changyang Gong*(Corresponding author). Multi-Targeted and On-Demand Non-Coding RNA Regulation Nanoplatform against Metastasis and Recurrence of Triple-Negative Breast Cancer.Small.2023, 19(23): 2207576 SCI
[20]Jin Yang, Liping Bai, Meiling Shen, Xinyu Gou, Zhongzheng Xiang, Shuang Ma, Qinjie Wu, and Changyang Gong*(Corresponding author). A Multiple Stimuli-Responsive NanoCRISPR Overcomes Tumor Redox Heterogeneity to Augment Photodynamic Therapy.ACS Nano.2023, 17(12): 11414-11426 SCI
[21]Wen Yang#(co-first author), Ning Wang#(co-first author), Jin Yang, Chao Liu, Shuang Ma, Xiye Wang, Wenzhen Li, Meiling Shen, Qinjie Wu*, Changyang Gong*(Corresponding author).A Multifunctional ‘Golden Cicada’ Nanoplatform Break the Thermoresistance Barrier to Launch Cascade Augmented Synergistic Effects of Photothermal/Gene Therapy.Journal of Nanobiotechnology.2023, 21: 228 SCI
[22]Cailing Gan#(co-first author), Yan Wang#(co-first author), Zhongzheng Xiang, Hongyao Liu, Zui Tan, Yuting Xie, Yuqin Yao, Liang Ouyang, Changyang Gong*(Corresponding author), Tinghong Ye*.Niclosamide-loaded nanoparticles (Ncl-NPs) reverse pulmonary fibrosis in vivo and in vitro.Journal of Advanced Research.2023, 51: 109-120 SCI
[23]Tao He#(co-first author), Yiling Shi#(co-first author), Xiaorong Kou, Meiling Shen, Xiuqi Liang, Xinchao Li, Rui Wu, Qinjie Wu, Changyang Gong*(Corresponding author).Antigenicity and adjuvanticity co-reinforced personalized cell vaccines based on self-adjuvanted hydrogel for post-surgical cancer vaccination.Biomaterials.2023, 301, 122218 SCI
[24]Xiaorong Kou#(co-first author), Tao He#(co-first author), Miaomiao Zhang, Xinyue Wu, Xinchao Li, Rui Luo, Rui Wu, Xinyu Gou, Meiling Shen, Qinjie Wu, Changyang Gong*(Corresponding author).A Multivalent Personalized Vaccine Orchestrating Two-Signal Activation Rebuilds the Bridge between Innate and Adaptive Anti-tumor Immunity.Small Methods.2023, 7(10): 2300019 SCI
[25]Xianzhou Huang, Lu Li, Chunqing Ou, Meiling Shen, Xinchao Li, Miaomiao Zhang, Rui Wu, Xiaorong Kou, Ling Gao, Furong Liu, Rui Luo, Qinjie Wu, Changyang Gong*(Corresponding author).Tumor Environment Regression Therapy Implemented by Switchable Prune-to-Essence Nanoplatform Unleashed Systemic Immune Responses.Advanced Science.2023, 10(35): 2303715 SCI
[26]Rui Luo, Chunqing Ou, Xinchao Li, Yanfang Wang, Wei Du, Gaolin Liang*(Corresponding author), Changyang Gong*(Corresponding author).An Acidity-Initiated Self-Assembly/Disassembly Nanoprobe to Switch on Fluorescence for Tumor Targeted Near-Infrared Imaging.Nano Letters.2022, 22(1): 151-156. SCI
[27]Xinchao Li, Rui Luo, Xiuqi Liang, Qinjie Wu, Changyang Gong*(Corresponding author).Recent advances in enhancing reactive oxygen species based chemodynamic therapy.Chinese Chemical Letters 2022, 33(5): 2213-2230 SCI
[28]Dengshen Zhang, Jun Shi, Guiyou Liang, Daxing Liu, Jian Zhang, Sisi Pan, Yuanfu Lu, Qin Wu, Changyang Gong*(Corresponding author), Yingqiang Guo*.miR-16-5p is a Novel Mediator of Venous Smooth Muscle Phenotypic Switching. Journal of Cardiovascular Translational Research.2022, 15(4): 876-889 SCI
[29]Zichao Luo#(co-first author), Xiuqi Liang#(co-first author), Tao He, Xian Qin, Xinchao Li, Yueshan Li, Lu Li, Xian Jun Loh, Changyang Gong*(Corresponding author), Xiaogang Liu*. Lanthanide-Nucleotide Coordination Nanoparticles for STING Activation.Journal of the American Chemical Society.2022, 144(36), 16366–16377 SCI
[30]Xi Yang, Yuanfeng Wei, Lingnan Zheng, Jia You, Huawei Li, Ling Gao, Changyang Gong*(Corresponding author), Cheng Yi*. Polyethyleneimine-based immunoadjuvants for designing cancer vaccines.Journal of Materials Chemistry B 2022, 10(40): 8166-8180 SCI
[31]Changyang Gong*。 Multifunctional Light-Activatable Nanocomplex Conducting Temperate-Heat Photothermal Therapy to Avert Excessive Inflammation and Trigger Augmented Immunotherapy Multifunctional Light-Activatable Nanocomplex Conducting Temperate-Heat Photothermal Therapy to Avert Excessive Inflammation and Trigger Augmented Immunotherapy. Biomaterials. 2022, 290, 121815 SCI
[32]Songlin Gong#(co-first author), Xiuqi Liang#(co-first author), Miaomiao Zhang, Lu Li, Tao He, Yuan Yuan, Xinchao Li, Furong Liu, Xi Yang, Meilin Shen, Qinjie Wu*, Changyang Gong*(Corresponding author).Tumor Microenvironment-Activated Hydrogel Platform with Programmed Release Property Evokes a Cascade-Amplified Immune Response against Tumor Growth, Metastasis and Recurrence.Small.2022, 18(50): 2107061 SCI
[33]Yang, Xi; You, Jia; Wei, Yuanfeng; Li, Huawei; Gao, Ling; Guo, Qing; Huang, Ying; Gong, Changyang*; Yi, Cheng*.Emerging nanomaterials applied for tackling the COVID-19 cytokine storm.Journal of Materials Chemistry B, 2021, 9(39): 8185-8201.
[34]Yang, Jin; Song, Linjiang; Shen, Meiling; Gou, Xinyu; Bai, Liping; Wang, Li; Zhang, Wenli; Wu, Qinjie; Gong, Changyang*.Hierarchically Responsive Tumor-Microenvironment-Activated Nano-Artificial Virus (TMAN) for Precise Exogenous and Endogenous Apoptosis Coactivation.Advanced Functional Materials, 2021, 31(37): 2104423.
[35]Yang, Jin; Li, Zhike; Shen, Meiling; Wang, Yan; Wang, Li; Li, Jiamiao; Yang, Wen; Li, Jie; Li, Haijun; Wang, Xinxin; Wu, Qinjie; Gong, Changyang*.Programmable Unlocking Nano-Matryoshka-CRISPR Precisely Reverses Immunosuppression to Unleash Cascade Amplified Adaptive Immune Response.Advanced Science, 2021, 8(13): 2100292.
[36]Huang, Xianzhou; Ou, Chunqing; Shu, Yaqian; Wang, Yan; Gong, Songlin; Luo, Rui; Chen, Shouchun; Wu, Qinjie*; Gong, Changyang*.A self-sustained nanoplatform reverses TRAIL-resistance of pancreatic cancer through coactivating of exogenous and endogenous apoptotic pathway.Biomaterials, 2021, 272: 120795.
[37]Luo, Zichao; He, Tao; Liu, Peng; Yi, Zhigao; Zhu, Shunyao; Liang, Xiuqi; Kang, Entang; Gong, Changyang*; Liu, Xiaogang*.Self-Adjuvanted Molecular Activator (SeaMac) Nanovaccines Promote Cancer Immunotherapy.Advanced Healthcare Materials, 2021, 10(7): 2002080.
[38]Liu, Furong; Gong, Songlin; Shen, Meiling; He, Tao; Liang, Xiuqi; Shu, Yaqian; Wang, Xinxin; Ma, Shuang; Li, Xinchao; Zhang, Miaomiao; Wu, Qinjie*; Gong, Changyang*.A glutathione-activatable nanoplatform for enhanced photodynamic therapy with simultaneous hypoxia relief and glutathione depletion.Chemical Engineering Journal, 2021, 403: 126305.
[39]He, Tao; Liang, Xiuqi; Li, Lu; Gong, Songlin; Li, Xinchao; Zhang, Miaomiao; Zhu, Shunyao; Xiao, Haitao; Wu, Qinjie*; Gong, Changyang*.A spontaneously formed and self-adjuvanted hydrogel vaccine triggers strong immune responses.Materials and Design, 2021, 197: 109232.
[40]Liu, Chao; Wang, Ning; Luo, Rui; Li, Lu; Yang, Wen; Wang, Xiye; Shen, Meiling; Wu, Qinjie; Gong, Changyang.A programmable hierarchical-responsive nanoCRISPR elicits robust activation of endogenous target to treat cancer.Theranostics, 2021, 11(20): 9833-9846.
[41]Liang, Xiuqi; Li, Lu; Li, Xinchao; He, Tao; Gong, Songlin; Zhu, Shunyao; Zhang, Miaomiao; Wu, Qinjie*; Gong, Changyang*.A spontaneous multifunctional hydrogel vaccine amplifies the innate immune response to launch a powerful antitumor adaptive immune response.Theranostics, 2021, 11(14): 6936-6949.
[42]Wang, Ning; Liu, Chao; Lu, Zhenghao; Yang, Wen; Li, Lu; Gong, Songlin; He, Tao; Ou, Chunqing; Song, Linjiang; Shen, Meiling; Wu, Qinjie; Gong, Changyang*.Multistage Sensitive NanoCRISPR Enable Efficient Intracellular Disruption of Immune Checkpoints for Robust Innate and Adaptive Immune Coactivation.Advanced Functional Materials, 2020, 30(45): 2004940.
[43]Yang, Xi; Gao, Ling; Guo, Qing; Li, Yongjiang; Ma, Yue; Yang, Ju; Gong, Changyang*; Yi, Cheng*.Nanomaterials for radiotherapeutics-based multimodal synergistic cancer therapy.Nano Research, 2020, 13(10): 2579-2594.
[44]Xiangrong, Song; Chao, Liu; Ning, Wang; Hai, Huang; Siyan, He; Changyang, Gong; Yuquan, Wei.Delivery of CRISPR/Cas systems for cancer gene therapy and immunotherapy.Advanced Drug Delivery Reviews, 2020.
[45]Yang, Suleixin; Ou, Chunqing; Wang, Li; Liu, Xiaowei; Yang, Jin; Wang, Xinxin; Wang, Meilin; Shen, Meiling; Wu, Qinjie; Gong, Changyang*.Virus-esque nucleus-targeting nanoparticles deliver trojan plasmid for release of anti-tumor shuttle protein.Journal of Controlled Release, 2020, 320: 253-264.
[46]Jiang, Fan; Zhu, Yunqi; Gong, Changyang*; Wei, Xin*.Atherosclerosis and Nanomedicine Potential: Current Advances and Future Opportunities.Current Medicinal Chemistry, 2020, 27(21): 3534-3554.
[47]Wang, Yan; Wang, Xinxin; Zhang, Jing; Wang, Li; Ou, Chunqing; Shu, Yaqian; Wu, Qinjie; Ma, Guolin*; Gong, Changyang*.Gambogic acid-encapsulated polymeric micelles improved therapeutic effects on pancreatic cancer.Chinese Chemical Letters, 2019, 30(4): 885-888.
[48]Wang, Ning; Liu, Chao; Wang, Xinxin; He, Tao; Li, Lu; Liang, Xiuqi; Wang, Li; Song, Linjiang; Wei, Yuquan; Wu, Qinjie*; Gong, Changyang*.Hyaluronic Acid Oligosaccharides Improve Myocardial Function Reconstruction and Angiogenesis against Myocardial Infarction by Regulation of Macrophages.Theranostics, 2019, 9(7): 1980-1992.
[49]Luo, Lijia; Liu, Chuang; He, Tao; Zeng, Leyong; Xing, Jie; Xia, Yuanzhi; Pan, Yuanwei; Gong, Changyang*; Wu, Aiguo*.Engineered fluorescent carbon dots as promising immune adjuvants to efficiently enhance cancer immunotherapy.Nanoscale, 2018, 10(46): 22035-22043.
[50]Song, Linjiang; Liang, Xiuqi; Yang, Suleixin; Wang, Ning; He, Tao; Wang, Yan; Zhang, Lan; Wu, Qinjie; Gong, Changyang*.Novel polyethyleneimine-R8-heparin nanogel for high-efficiency gene delivery in vitro and in vivo.Drug Delivery, 2018, 25(1): 122-131.
[51]Li, Ling; Yang, Suleixin; Song, Linjiang; Zeng, Yan; He, Tao; Wang, Ning; Yu, Chuan; Yin, Tao; Liu, Li; Wei, Xiawei; Wu, Qinjie; Wei, Yuquan; Yang, Li; Gong, Changyang*.An Endogenous Vaccine Based on Fluorophores and Multivalent Immunoadjuvants Regulates Tumor Micro-Environment for Synergistic Photothermal and Immunotherapy.Theranostics, 2018, 8(3): 860-873.
[52]Yang, Xi; Li, Zhaojun; Wu, Qinjie; Chen, Shouchun; Yi, Cheng*; Gong, Changyang*.TRAIL and curcumin codelivery nanoparticles enhance TRAIL-induced apoptosis through upregulation of death receptors.Drug Delivery, 2017, 24(1): 1526-1536.
[53]Luo, Zichao; Wu, Qinjie; Yang, Chengbiao; Wang, Huaimin; He, Tao; Wang, Youzhi; Wang, Zhongyan; Chen, Hao; Li, Xingyi*; Gong, Changyang*; Yang, Zhimou*.A Powerful CD8(+) T-Cell Stimulating D-Tetra-Peptide Hydrogel as a Very Promising Vaccine Adjuvant.Advanced Materials, 2017, 29(5): 1601776.
[54]Li, Ling; Song, Linjiang; Liu, Xiaowei; Yang, Xi; Li, Xia; He, Tao; Wang, Ning; Yang, Suleixin; Yu, Chuan; Yin, Tao; Wen, Yanzhu; He, Zhiyao; Wei, Xiawei; Su, Weijun; Wu, Qinjie; Yao, Shaohua*; Gong, Changyang*; Wei, Yuquan*.Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice.ACS Nano, 2017, 11(1): 95-111.
[55]Li, Ling; Li, Xia; Wu, Yuzhe; Song, Linjiang; Yang, Xi; He, Tao; Wang, Ning; Yang, Suleixin; Zeng, Yan; Wu, Qinjie; Qian, Zhiyong; Wei, Yuquan; Gong, Changyang*.Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy.Theranostics, 2017, 7(6): 1633-1649.
[56]He, Tao; Zou, Chang; Song, Linjiang; Wang, Ning; Yang, Suleixin; Zeng, Yan; Wu, Qinjie; Zhang, Wenli; Chen, Yingtai*; Gong, Changyang*.Improving Antiadhesion Effect of Thermosensitive Hydrogel with Sustained Release of Tissue-type Plasminogen Activator in a Rat Repeated-Injury Model.ACS Applied Materials & Interfaces, 2016, 8(49): 33514-33520.
[57]Li, Ling; Song, Linjiang; Yang, Xi; Li, Xia; Wu, Yuzhe; He, Tao; Wang, Ning; Yang, Suleixin; Zeng, Yan; Yang, Li; Wu, Qinjie; Wei, Yuquan; Gong, Changyang*.Multifunctional "core-shell" nanoparticles-based gene delivery for treatment of aggressive melanoma.Biomaterials, 2016, 111: 124-137.
[58]Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li*; Wu, Qinjie*; Gong, Changyang*.Peritoneal adhesion prevention with a biodegradable and injectable N, O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model.Scientific Reports, 2016, 6(1): 37600.
[59]Wang, Huaimin; Luo, Zichao; Wang, Youzhi; He, Tao; Yang, Chengbiao; Ren, Chunhua; Ma, Linsha; Gong, Changyang*; Li, Xingyi*; Yang, Zhimou*.Enzyme-Catalyzed Formation of Supramolecular Hydrogels as Promising Vaccine Adjuvants.Advanced Functional Materials, 2016, 26(11): 1822-1829.
[60]Wang, Ning; He, Tao; Shen, Yangmei; Song, Linjiang; Li, Ling; Yang, Xi; Li, Xia; Pang, Mengru; Su, Weijun; Liu, Xinyu*; Wu, Qinjie*; Gong, Changyang*.Paclitaxel and Tacrolimus Coencapsulated Polymeric Micelles That Enhance the Therapeutic Effect of Drug-Resistant Ovarian Cancer.ACS Applied Materials & Interfaces, 2016, 8(7): 4368-4377.
[61]Sun, Lu; Wu, Qinjie; Peng, Feng; Liu, Lei; Gong, Changyang*.Strategies of polymeric nanoparticles for enhanced internalization in cancer therapy.Colloids and Surfaces B: Biointerfaces , 2015, 135: 56-72.
[62]Wu, Qinjie; Wang, Ning; He, Tao; Shang, Jinfeng; Li, Ling; Song, Linjiang; Yang, Xi; Li, Xia; Luo, Na; Zhang, Wenli; Gong, Changyang*.Thermosensitive hydrogel containing dexamethasone micelles for preventing postsurgical adhesion in a repeated-injury model.Scientific Reports, 2015, 5(1): 13553.
[63]Zhang, Wenli; Cui, Tao; Liu, Lei*; Wu, Qinjie; Sun, Lu; Li, Ling; Wang, Ning; Gong, Changyang*(Corresponding author).Improving Anti-Tumor Activity of Curcumin by Polymeric Micelles in Thermosensitive Hydrogel System in Colorectal Peritoneal Carcinomatosis Model.Journal of Biomedical Nanotechnology, 2015, 11(7): 1173-1182.
[64]Yang, Xi; Li, Zhaojun; Wang, Ning; Li, Ling; Song, Linjiang; He, Tao; Sun, Lu; Wang, Zhihan; Wu, Qinjie; Luo, Na; Yi, Cheng*; Gong, Changyang.Curcumin-Encapsulated Polymeric Micelles Suppress the Development of Colon Cancer In Vitro and In Vivo.Scientific Reports, 2015, 5(1): 10322.
[65]Li, Ling; Wei, Yuquan; Gong, Changyang*(Corresponding author). Polymeric Nanocarriers for Non-Viral Gene Delivery. Journal of Biomedical Nanotechnology, 2015, 11(5): 739-770.
[66]Gao, Xiang; Wang, Bilan; Wu, Qinjie; Wei, Xiawei; Zheng, Fengjin; Men, Ke; Shi, Huashan; Huang, Ning; Wei, Yuquan; Gong, Changyang*.Combined Delivery and Anti-Cancer Activity of Paclitaxel and Curcumin Using Polymeric Micelles.Journal of Biomedical Nanotechnology, 2015, 11(4): 578-589.
[67]Gou, Qiheng; Liu, Lei; Wang, Chunting; Wu, Qinjie; Sun, Lu; Yang, Xi; Xie, Yuxin; Li, Ping*; Gong, Changyang.Polymeric nanoassemblies entrapping curcumin overcome multidrug resistance in ovarian cancer.Colloids and Surfaces B: Biointerfaces , 2015, 126: 26-34.
[68]Chen, Yishan; Wu, Qinjie; Song, Linjiang; He, Tao; Li, Yuchen; Li, Ling; Su, Weijun; Liu, Lei*; Qian, Zhiyong; Gong, Changyang.Polymeric Micelles Encapsulating Fisetin Improve the Therapeutic Effect in Colon Cancer.ACS Applied Materials & Interfaces, 2015, 7(1): 534-542.
[69]Zhang, Nannan; Liu, Shichang; Wang, Ning; Deng, Senyi; Song, Linjiang; Wu, Qinjie; Liu, Lei; Su, Weijun; Wei, Yuquan; Xie, Yongmei*; Gong, Changyang.Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway.Nanoscale, 2015, 7(6): 2609-2624.
[70]Deng, Senyi; Wu, Qinjie; Zhao, Yuwei; Zheng, Xin; Wu, Ni; Pang, Jing; Li, Xuejing; Bi, Cheng; Liu, Xinyu; Yang, Li; Liu, Lei; Su, Weijun; Wei, Yuquan; Gong, Changyang*.Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells.Nanoscale, 2015, 7(12): 5270-5280.
[71]Zhang, Wenli; Wu, Qinjie; Li, Ling; Cui, Tao; Sun, Lu; Wang, Ning; Liu, Lei*; Li, Xinyu; Gong, Changyang.Prevention of desiccation induced postsurgical adhesion by thermosensitive micelles.Colloids and Surfaces B: Biointerfaces , 2014, 122: 309-315.
[72]He, Sha-Sha; Wu, Qin-Jie; Gong, Chang Yang; Luo, Shun-Tao; Zhang, Shuang; Li, Meng; Lu, Lian; Wei, Yu-Quan; Yang, Li*.Enhanced efficacy of combination therapy with adeno-associated virus-delivered pigment epithelium-derived factor and cisplatin in a mouse model of Lewis lung carcinoma.Molecular Medicine Reports, 2014, 9(6): 2069-2076.
[73]Li, Ling; Wang, Ning; Jin, Xun; Deng, Rui; Nie, Shihong; Sun, Lu; Wu, Qinjie; Wei, Yuquan; Gong, Changyang*(Corresponding author).Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention.Biomaterials, 2014, 35(12): 3903-3917.
[74]Yang, Xi; Cao, Dan; Wang, Ning; Sun, Lu; Li, Ling; Nie, Shihong; Wu, Qinjie; Liu, Xinyu; Yi, Cheng; Gong, Changyang*.In Vitro and In Vivo Safety Evaluation of Biodegradable Self-Assembled Monomethyl Poly(Ethylene Glycol)-Poly(epsilon-Caprolactone)-Poly(Trimethylene Carbonate) Micelles.Journal of Pharmaceutical Sciences, 2014, 103(1): 305-313.
[75]Wu, Qinjie; Li, Ling; Wang, Ning; Gao, Xiang; Wang, Bilan; Liu, Xinyu; Qian, Zhiyong; Wei, Yuquan; Gong, Changyang*.Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion.International Journal of Nanomedicine, 2014, 9: 727-734.
[76]Liu, Yuanyuan; Chang, Ying; Yang, Chao; Sang, Zitai; Yang, Tao; Ang, Wei; Ye, Weiwei; Wei, Yuquan; Gong, Changyang*(Corresponding author); Luo, Youfu.Biodegradable nanoassemblies of piperlongumine display enhanced anti-angiogenesis and anti-tumor activities.Nanoscale, 2014, 6(8): 4325-4337.
[77]Sun, Lu; Deng, Xiaohui; Yang, Xi; Li, Zhaojun; Wang, Zhihan; Li, Ling; Wu, Qinjie; Peng, Feng; Liu, Lei; Gong, Changyang*.Co-delivery of doxorubicin and curcumin by polymeric micelles for improving antitumor efficacy on breast carcinoma.RSC Advances, 2014, 4(87): 46737-46750.
[78]Yang, Xi; Yi, Cheng; Luo, Na; Gong, Changyang*.Nanomedicine to Overcome Cancer Multidrug Resistance.Current Drug Metabolism, 2014, 15(6): 632-649.
[79]Wu, Qinjie; Li, Guoyou; Deng, Senyi; Ouyang, Liang; Li, Ling; Liu, Lei; Luo, Na; Song, Xiangrong; He, Gu*; Gong, Changyang;* (Corresponding author), Wei, Yuquan. Enhanced antitumor activity and mechanism of biodegradable polymeric micelles-encapsulated chetomin on both transgenic zebrafish and mouse models.Nanoscale, 2014, 6(20): 11940-11952.
[80]Gao Xiang, et al., ChangYang Gong*(Corresponding author). Improving anti-tumor activity by polymeric micelles encapsulating paclitaxel and curcumin simultaneously. J Biomed Nanotechnol, 2014, in press. IF=7.578
[81]Wu, Qinjie; Deng, Senyi; Li, Ling; Sun, Lu; Yang, Xi; Liu, Xinyu; Liu, Lei; Qian, Zhiyong; Wei, Yuquan; Gong, Changyang*(Corresponding author).Biodegradable polymeric micelle-encapsulated quercetin suppresses tumor growth and metastasis in both transgenic zebrafish and mouse models.Nanoscale, 2013, 5(24): 12480-12493.
[82]Gong, Chang Yang; Wu, Qin Jie; Liao, Jin Feng; Qi, Ting Ting; Yang, Bing; Wang, Yu Jun; Guo, Gang; Luo, Feng; Zhao, Xia; Wei, Yu Quan; Qian, Zhi Yong*.Prevention of Postsurgical Cauterization-Induced Peritoneal Adhesions by Biodegradable and Thermosensitive Micelles.Journal of Biomedical Nanotechnology, 2013, 9(12): 1984-1995.
[83]Gong, ChangYang; Wu, QinJie; Wang, YuJun; Zhang, DouDou; Luo, Feng; Zhao, Xia; Wei, YuQuan; Qian, ZhiYong*.A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing.Biomaterials, 2013, 34(27): 6377-6387.
[84]Long, Qida; Xie, Yao; Huang, Yanqing; Wu, Qinjie; Zhang, HeCheng; Xiong, Shaoquan; Liu, Yingwei; Chen, Lijuan; Wei, Yuquan; Zhao, Xia*; Gong, Changyang.Induction of Apoptosis and Inhibition of Angiogenesis by PEGylated Liposomal Quercetin in Both Cisplatin-Sensitive and Cisplatin-Resistant Ovarian Cancers.Journal of Biomedical Nanotechnology, 2013, 9(6): 965-975.
[85]Gong, Changyang*(Corresponding author); Deng, Senyi; Wu, Qinjie; Xiang, Mingli; Wei, Xiawei; Li, Ling; Gao, Xiang; Wang, Bilan; Sun, Lu; Chen, Yishan; Li, Yuchen; Liu, Lei; Qian, Zhiyong; Wei, Yuquan.Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles.Biomaterials, 2013, 34(4): 1413-1432.
[86]Gong, Changyang; Yang, Tao; Yang, Xiaoyan; Liu, Yuanyuan; Ang, Wei; Tang, Jianying; Pi, Weiyi; Xiong, Li; Chang, Ying; Ye, WeiWei; Wang, Zhenling*; Luo, Youfu; Zhao, Xia; Wei, Yuquan.Carrier-free nanoassemblies of a novel oxazolidinone compound FYL-67 display antimicrobial activity on methicillin-resistant Staphylococcus aureus.Nanoscale, 2013, 5(1): 275-283.
[87]Liu, Lei; Wu, Qinjie; Ma, Xuelei; Xiong, Dake; Gong, Changyang*; Qian, Zhiyong; Zhao, Xia; Wei, Yuquan.Camptothecine encapsulated composite drug delivery system for colorectal peritoneal carcinomatosis therapy: Biodegradable microsphere in thermosensitive hydrogel.Colloids and Surfaces B: Biointerfaces , 2013, 106: 93-101.
[88]Liu, Lei; Sun, Lu; Wu, Qinjie; Guo, Wenhao; Li, Ling; Chen, YiShan; Li, Yuchen; Gong, Changyang*; Qian, Zhiyong; Wei, Yuquan.Curcumin loaded polymeric micelles inhibit breast tumor growth and spontaneous pulmonary metastasis.International Journal of Pharmaceutics, 2013, 443(1-2): 175-182.
[89]Gong, C.; Qi, T.; Wei, X.; Qu, Y.; Wu, Q.; Luo, F.; Qian, Z.*.Thermosensitive Polymeric Hydrogels As Drug Delivery Systems.Current Medicinal Chemistry, 2013, 20(1): 79-94.
[90]Gao, Xiang; Deng, Xiaohui; Wei, Xiawei; Shi, Huashan; Wang, Fengtian; Ye, Tinghong; Shao, Bin; Nie, Wen; Li, Yuli; Luo, Min; Gong, Changyang*; Huang, Ning.Novel thermosensitive hydrogel for preventing formation of abdominal adhesions.International Journal of Nanomedicine, 2013, 8: 2453-2463.
[91]Gong, Changyang*(Corresponding author); Xie, Yongmei; Wu, Qinjie; Wang, Yujun; Deng, Senyi; Xiong, Dake; Liu, Lei; Xiang, Mingli; Qian, Zhiyong; Wei, Yuquan.Improving anti-tumor activity with polymeric micelles entrapping paclitaxel in pulmonary carcinoma.Nanoscale, 2012, 4(19): 6004-6017.
[92]Gong, ChangYang; Yang, Bing; Qian, ZhiYong*; Zhao, Xia; Wu, QinJie; Qi, XiaoRong; Wang, YuJun; Guo, Gang; Kan, Bing; Luo, Feng; Wei, YuQuan.Improving intraperitoneal chemotherapeutic effect and preventing postsurgical adhesions simultaneously with biodegradable micelles.Nanomedicine: Nanotechnology, Biology and Medicine , 2012, 8(6): 963-973.
[93]Lei, Na; Gong, ChangYang+(co-first author); Qian, ZhiYong*; Luo, Feng; Wang, Cheng; Wang, HeLan; Wei, YuQuan.Therapeutic application of injectable thermosensitive hydrogel in preventing local breast cancer recurrence and improving incision wound healing in a mouse model.Nanoscale, 2012, 4(18): 5686-5693.
[94]Gong, ChangYang; Wang, Cheng; Wang, YuJun; Wu, QinJie; Zhang, DouDou; Luo, Feng; Qian, ZhiYong*.Efficient inhibition of colorectal peritoneal carcinomatosis by drug loaded micelles in thermosensitive hydrogel composites.Nanoscale, 2012, 4(10): 3095-3104.
[95]Zhang, Qiong-wen; Liu, Lei*; Gong, Chang-yang; Shi, Hua-shan; Zeng, Yun-hui; Wang, Xiao-ze; Zhao, Yu-wei; Wei, Yu-quan.Prognostic Significance of Tumor-Associated Macrophages in Solid Tumor: A Meta-Analysis of the Literature.PLos One, 2012, 7(12): e50946.
[96]Shi, Hua-shan; Gong, Chang-yang; Zhang, Hai-long; Wang, Yong-sheng*; Zhang, Jing; Luo, Zi-chao; Qian, Zhi-yong; Wei, Yu-quan; Yang, Li.Novel vaccine adjuvant LPS-Hydrogel for truncated basic fibroblast growth factor to induce antitumor immunity.Carbohydrate Polymers, 2012, 89(4): 1101-1109.
[97]Li, Jing*; Gong, Changyang; Feng, Xiaodong; Zhou, Xikun; Xu, Xiaoping; Xie, Liang; Wang, Ruinan; Zhang, Dunfang; Wang, Hui; Deng, Peng; Zhou, Min; Ji, Ning; Zhou, Yu; Wang, Yun; Wang, Zhiyong; Liao, Ga; Geng, Ning; Chu, Liangyin; Qian, Zhiyong; Wang, Zhi; Chen, Qianming.Biodegradable Thermosensitive Hydrogel for SAHA and DDP Delivery: Therapeutic Effects on Oral Squamous Cell Carcinoma Xenografts.PLos One, 2012, 7(4): e33860.
[98]Wu, Qin Jie; Gong, Chang Yang; Luo, Shun Tao; Zhang, Dong Mei; Zhang, Shuang; Shi, Hua Shan; Lu, Lian; Yan, Heng Xiu; He, Sha Sha; Li, Dan Dan; Yang, Li*; Zhao, Xia; Wei, Yu Quan。AAV-mediated human PEDF inhibits tumor growth and metastasis in murine colorectal peritoneal carcinomatosis model.BMC Cancer, 2012, 12: 129.
[99]Yang, Bing; Gong, ChangYang; Zhao, Xia; Zhou, ShengTao; Li, ZhengYu; Qi, XiaoRong; Zhong, Qian; Luo, Feng; Qian, ZhiYong*.Preventing postoperative abdominal adhesions in a rat model with PEG-PCL-PEG hydrogel.International Journal of Nanomedicine, 2012, 7: 547-557.
[100]Xie, Yao*; Long, Qida; Wu, QinJie; Shi, Shuai; Dai, Mei; Liu, Yingwei; Liu, Lei; Gong, Changyang; Qian, Zhiyong; Wei, Yuquan; Zhao, Xia.Improving therapeutic effect in ovarian peritoneal carcinomatosis with honokiol nanoparticles in a thermosensitive hydrogel composite.RSC Advances, 2012, 2(20): 7759-7771.
[101]Wu, Qin Jie; Zhu, Xue Chen; Xiao, Xiong; Wang, Pan; Xiong, Da Ke; Gong, Chang Yang*; Wang, Yong Sheng; Yang, Li; Wei, Yu Quan.A novel vaccine delivery system: Biodegradable nanoparticles in thermosensitive hydrogel.Growth Factors, 2011, 29(6): 290-297.
[102]Gong, ChangYang; Wang, YuJun; Wang, XiuHong; Wei, XiaWei; Wu, QinJie; Wang, BiLan; Dong, PengWei; Chen, LiJuan*; Luo, Feng; Qian, ZhiYong.Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic drug delivery, part 2: in vitro and in vivo toxicity evaluation.Journal of Nanoparticle Research, 2011, 13(2): 721-731.
[103]Yang, Bing; Gong, Chang Yang; Qian, Zhi Yong*; Zhao, Xia; Li, Zheng Yu; Zhou, Sheng Tao; Qi, Xiao Rong; Zhong, Qian; Luo, Feng; Wei, Yu Quan.Prevention of abdominal adhesion formation by thermosensitive PECE-hydrogel in a rat uterine horn model.Journal of Biomedical Materials Research Part B: Applied Biomaterials , 2011, 96B(1): 57-66.
[104]Wang, Yongsheng*; Gong, Changyang; Yang, Li; Wu, Qinjie; Shi, Shuai; Shi, Huashan; Qian, Zhiyong; Wei, Yuquan.5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in mice.BMC Cancer, 2010, 10: 402.
[105]Gong, ChangYang; Wei, XiaWei; Wang, XiuHong; Wang, YuJun; Guo, Gang; Mao, YongQiu; Luo, Feng; Qian, ZhiYong*.Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic honokiol delivery: I. Preparation and characterization.Nanotechnology, 2010, 21(21): 215103.
[106]Gou, MaLing; Gong, ChangYang; Zhang, Juan; Wang, XiuHong; Wang, XianHuo; Gu, YingChun; Guo, Gang; Chen, LiJuan; Luo, Feng; Zhao, Xia; Wei, YuQuan; Qian, ZhiYong*.Polymeric matrix for drug delivery: Honokiol-loaded PCL-PEG-PCL nanoparticles in PEG-PCL-PEG thermosensitive hydrogel.Journal of Biomedical Materials Research Part A, 2010, 93A(1): 219-226.
[107]Yin, HongBo; Gong, ChangYang; Shi, Shuai; Liu, XuYang*; Wei, YuQuan; Qian, ZhiYong.Toxicity Evaluation of Biodegradable and Thermosensitive PEG-PCL-PEG Hydrogel as a Potential In Situ Sustained Ophthalmic Drug Delivery System.Journal of Biomedical Materials Research Part B: Applied Biomaterials , 2010, 92B(1): 129-137.
[108]Fang, Fang; Gong, ChangYang+(co-first author); Qian, ZhiYong*; Zhang, XiaoNing; Gou, MaLing; You, Chao; Zhou, LiangXue; Liu, JiaGang; Zhang, Yu; Guo, Gang; Gu, YingChun; Luo, Feng; Chen, LiJuan; Zhao, Xia; Wei, YuQuan.Honokiol Nanoparticles in Thermosensitive Hydrogel: Therapeutic Effects on Malignant Pleural Effusion.ACS Nano, 2009, 3(12): 4080-4088.
[109]Gong, Chang-Yang; Shi, Shuai; Peng, Xin-Yun; Kan, Bing; Yang, Li*; Huang, Mei-Juan; Luo, Feng; Zhao, Xia; Wei, Yu-Quan; Qian, Zhi-Yong.Biodegradable thermosensitive injectable PEG-PCL-PEG hydrogel for bFGF antigen delivery to improve humoral immunity.Growth Factors, 2009, 27(6): 377-383.
[110]Gong, Chang Yang; Shi, Shuai; Dong, Peng Wei; Yang, Bing; Qi, Xiao Rong; Guo, Gang; Gu, Ying Chun; Zhao, Xia; Wei, Yu Quan; Qian, Zhi Yong*.Biodegradable In Situ Gel-Forming Controlled Drug Delivery System Based on Thermosensitive PCL-PEG-PCL Hydrogel: Part 1-Synthesis, Characterization, and Acute Toxicity Evaluation.Journal of Pharmaceutical Sciences, 2009, 98(12): 4684-4694.
[111]Gong, ChangYang; Shi, Shuai; Wu, Lan; Gou, MaLing; Yin, QinQin; Guo, QingFa; Dong, PengWei; Zhang, Fan; Luo, Feng; Zhao, Xia; Wei, YuQuan; Qian, ZhiYong*.Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel. Part 2: Sol-gel-sol transition and drug delivery behavior.Acta Biomaterialia, 2009, 5(9): 3358-3370.
[112]Gong, Chang Yang; Wu, Qin Jie; Dong, Peng Wei; Shi, Shuai; Fu, Shao Zhi; Guo, Gang; Hu, Huo Zhen; Zhao, Xia; Wei, Yu Quan; Qian, Zhi Yong*.Acute Toxicity Evaluation of Biodegradable In Situ Gel-Forming Controlled Drug Delivery System Based on Thermosensitive PEG-PCL-PEG Hydrogel.Journal of Biomedical Materials Research Part B: Applied Biomaterials , 2009, 91B(1): 26-36.
[113]Gong, Chang Yang; Dong, Peng Wei; Shi, Shuai; Fu, Shao Zhi; Yang, Jin Liang; Guo, Gang; Zhao, Xia; Wei, Yu Quan; Qian, Zhi Yong*.Thermosensitive PEG-PCL-PEG Hydrogel Controlled Drug Delivery System: Sol-Gel-Sol Transition and In Vitro Drug Release Study.Journal of Pharmaceutical Sciences, 2009, 98(10): 3707-3717.
[114]Gong, ChangYang; Shi, Shuai; Wang, XiuHong; Wang, YuJun; Fu, ShaoZhi; Dong, PengWei; Chen, LiJuan; Zhao, Xia; Wei, YuQuan; Qian, ZhiYong*.Novel Composite Drug Delivery System for Honokiol Delivery: Self-Assembled Poly(ethylene glycol)-Poly(epsilon-caprolactone)-Poly(ethylene glycol) Micelles in Thermosensitive Poly(ethylene glycol)-Poly(epsilon-caprolactone)-Poly(ethylene glycol) Hydrogel.Journal of Physical Chemistry B, 2009, 113(30): 10183-10188.
[115]Gong, Chang Yang; Fu, Shao Zhi; Gu, Ying Chun; Liu, Cai Bing; Kan, Bing; Deng, Hong Xin; Luo, Feng; Qian, Zhi Yong*.Synthesis, Characterization, and Hydrolytic Degradation of Biodegradable Poly(ether ester)-Urethane Copolymers Based on epsilon-Caprolactone and Poly(ethylene glycol).Journal of Applied Polymer Science, 2009, 113(2): 1111-1119.
[116]Fang, Fang; Gong, Chang Yang; Dong, Peng Wei; Fu, Shao Zhi; Gu, Ying Chun; Guo, Gang; Zhao, Xia; Wei, Yu Quan; Qian, Zhi Yong*.Acute toxicity evaluation of in situ gel-forming controlled drug delivery system based on biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) copolymer.Biomedical Materials (Bristol), 2009, 4(2): 025002.
[117]Gong, Chang Yang; Shi, Shuai; Dong, Peng Wei; Zheng, Xiu Ling; Fu, Shao Zhi; Guo, Gang; Yang, Jing Liang*; Wei, Yu Quan; Qian, Zhi Yong.In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) copolymer.BMC Biotechnology, 2009, 9(1): 8.
[118]Gong, ChangYang; Shi, Shuai; Dong, PengWei; Kan, Bing; Gou, MaLing; Wang, XianHuo; Li, XingYi; Luo, Feng; Zhao, Xia; Wei, YuQuan; Qian, ZhiYong*.Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel.International Journal of Pharmaceutics, 2009, 365(1-2): 89-99.
[119]Liu, Cai Bing; Gong, Chang Yang; Huang, Mei Juan; Wang, Ji Wei; Pan, Yi Feng; De Zhang, Yang; Li, Guo Zheng; Gou, Ma Ling; Wang, Ke; Tu, Ming Jing; Wei, Yu Quan; Qian, Zhi Yong*.Thermo reversible gel-sol behavior of biodegradable PCL-PEG-PCL triblock copolymer in aqueous solutions.Journal of Biomedical Materials Research Part B: Applied Biomaterials , 2008, 84B(1): 165-175.
[120]Liu, CaiBing; Gong, ChangYang; Pan, YiFeng; Zhang, YangDe; Wang, JiWei; Huang, MeiJuan; Wang, YongSheng; Wang, Ke; Gou, MaLing; Tu, MingJing; Wei, YuQuan; Qian, ZhiYong*.Synthesis and characterization of a thermosensitive hydrogel based on biodegradable amphiphilic PCL-Pluronic (L35)-PCL block copolymers.Colloids and Surfaces A: Physicochemical and Engineering Aspects , 2007, 302(1-3): 430-438.
[121]Gong, ChangYang; Qian, ZhiYong*; Liu, CaiBing; Huang, MeiJuan; Gu, YingChun; Wen, YanJun; Kan, Bing; Wang, Ke; Dai, Mei; Li, XingYi; Gou, MaLing; Tu, MingJing; Wei, YuQuan.A thermosensitive hydrogel based on biodegradable amphiphilic poly(ethylene glycol)-polycaprolactone-poly(ethylene glycol) block copolymers.Smart Materials and Structures, 2007, 16(3): 927-933.
代表性中文论文:
[1]巩长旸, 顾迎春, 谢震, 谢希惠, 刘彩兵, 阚兵, 涂铭旌, 魏于全, 钱志勇. 一种可生物降解温度敏感型聚乙二醇-聚己内酯-聚乙二醇水凝胶的合成和表征[J]. 生物医学工程学杂志, 2008, (05): 1121-1125.
[2]巩长旸, 顾迎春, 刘彩兵, 阚兵, 苟马玲, 邓洪新, 涂铭旌, 魏于全, 钱志勇. 温度敏感型PCL-Pluronic-PCL水凝胶的合成与性能[J]. 高分子材料科学与工程, 2007, (04): 86-88+93.
[3]苟马玲, 谢震, 王辉, 巩长旸, 涂铭旌, 钱志勇. 采用化学共沉淀法制备纳米磁流体[J]. 华西医学, 2007, (02): 343-344.
[4]赖庆柯,张永奎,梁斌,巩长旸. 酸性Fe(Ⅲ)溶液催化氧化S(Ⅳ)的研究[J]. 环境科学学报, 2004, (06): 1091-1097.
荣誉奖励:
1. 2013年,获全国百篇优秀博士生论文提名奖。
2. 2012年,获四川省百篇优秀博士生论文。
3. 2015年,入选中组部第二批“万人计划”青年拔尖人才。
4. 3篇论文入选ESI“高引用论文”。
——记四川大学生物治疗国家重点实验室巩长旸博士
“20世纪初,癌症的治愈率一直为零;二三十年代,随着外科手术治疗的诞生,癌症的存活率达到了25%;60年代,放疗和化疗的使用让癌症的治愈率上升到了38%;80年代,随着技术的进步,该数据又上升到了46%。综合这些治疗手段,目前癌症的存活率约为50%。这也预示着研发新的治疗手段迫在眉睫,生物治疗在这样的环境下应运而生。”2015(第五届)抗体药物及新药研发高峰会上,魏于全院士在主题演讲中说道。
生物治疗的靶向性,使其具有有的放矢的功效,顺应了个性化医疗和精准医疗的发展趋势。受到导师魏于全院士的影响,巩长旸也走上了生物治疗研究之路,他瞄准的重点是新型药物和基因传递系统。
年少立志 做有用的研究
“神奇”,在谈到对自己专业的初印象时,巩长旸用了这样一个词。
新型药物和基因传递系统,是近二三十年新兴起的一个研究领域。不同于传统的研究方向和学科方向,它是以药学、纳米技术、医学和生物材料学等学科交叉融合催生的“新人”。
“我感觉它是基础研究与应用研究并重的学科,也是现在生物医药领域研究的前沿和热点。”巩长旸说,“借助这个方向,我们可以将广泛的药物,包括小分子药物、基因、蛋白等精确地导入到肿瘤或其他病灶部位,尽量减少在身体其他器官的分布,使治疗发挥出更好的疗效,并且降低药物的系统毒性。”
能发挥这样的功效,在刚进入四川大学华西医院生物治疗国家重点实验室攻读硕士学位的巩长旸眼中,“神奇”二字并不夸张。那是2005年,巩长旸25岁,师从我国著名肿瘤治疗学家魏于全院士。
古人说山中无日月,对年轻的巩长旸来说,钻进一个新的世界,时间也很容易被忘却。2007年,他提前取得了攻读博士学位的资格,深受魏于全院士赏识。2008年,科技部“863”重点项目纳米生物材料研发正式启动,魏于全院士也将他带入项目中。以学生身份参与这么重要的项目,和那些学术上的大咖们一起工作,巩长旸很满足。“也是在那时候,我了解到什么是国家重大项目、重要需求”,他忍不住重复魏于全院士当年常对他说的那句话,“我们做科研,一定要按照国家的重大需求去解决实际问题,才能真正做出有用、有意义的东西。”
“生物和医学,是我从小就一直喜欢的方向。”1999年,19岁的巩长旸从沈阳来到成都。生活令人成长,正当他专心在四川大学学习生物工程专业知识的时候,一个噩耗传来——他的奶奶因为恶性肿瘤离开了。悲恸过后,巩长旸开始关心肿瘤治疗的相关信息,想要再通过自己的努力,真正在肿瘤领域做些有用的事。魏于全院士的话,戳中了他心中最柔软的地方,引起了他深刻的共鸣。从此,这句话成为他科研之旅中重要的指向标,再未动摇过。
来到生物治疗国家重点实验室后,巩长旸最先做的就是去了解这个实验室的研究动态。他发现,在新型的生物治疗手段上,无论是基因治疗、免疫治疗,还是小分子靶向药物治疗,都需要一些合适的载体,才能发挥出更好的疗效。“一是安全,二是有效”,巩长旸肯定地给出研究的两大重要前提。
2011年1月,科技部“重大新药创制”科技重大专项启动。这一次,巩长旸以项目组副组长的身份出现,成为“新型多烯紫杉醇水性制剂研发”的第一主研人员。
“为什么会有这方面的研究?因为现在很多科研机构和制药公司研制出的活性分子,不能直接应用于人体,必须经过一个制剂的过程,这个过程很困难。比如,很多活性分子虽然在体外有很好的药效,但由于疏水性强,很难形成均匀水基制剂,严重限制了其成药性。再比如现在肿瘤治疗中常用的一线药物紫杉醇,它本身是一种疏水性药物,为了制剂,会采用将聚氧乙烯蓖麻油和酒精1:1的混合液,这其实存在很大的安全隐患。”提起这些,巩长旸忧心忡忡,“聚氧乙烯蓖麻油会引起人的超敏反应,临床中会先给患者注射地塞米松等来预防过敏,但也增加了临床工作,应用起来不方便。”
巩长旸的研究就是为了解决这些问题。经过反复实验,他发现PEG/PCL胶束是一种较理想的纳米药物传递系统,并以此为“跳板”做了一系列出击。针对临床紫杉醇注射液中聚氧乙烯蓖麻油易引起过敏反应的问题,他采用PEG/PCL纳米胶束包载紫杉醇和多烯紫杉醇,获得了可静脉注射的新型紫杉烷纳米缓释制剂显著提高其抗肿瘤效果并降低毒副作用,为创制新型紫杉烷水基制剂提供了新选择。
在随后的研究中,他打起了姜黄素的主意。姜黄素也具有疏水性,他先是通过PEG/PCL纳米胶束单独包载姜黄素,制备出一种新型姜黄素纳米缓释制剂,为肿瘤转移的治疗提供了新思路,又开始考虑把姜黄素与其他药物作为一个共同体包载在PEG/PCL纳米胶束中。比如,与亲水性的阿霉素一起,可以在亲—疏水药物之间产生协同作用,显著提高肿瘤细胞对阿霉素的摄取;而与紫杉醇结合,可以在体内外显著提高紫杉醇的抗肿瘤效果,摒除紫杉醇耐药性的缺点。
“我们在前期制备过程中尽量不使用加高热、高速搅拌等剧烈的过程,也不使用有毒的有机溶剂,如果这些制剂要进行后期开发,就在最大程度上保障了安全性。看起来只是很小的工艺改进,我们也花了很大精力去探索。”巩长旸补充道。国际同行们显然也很认可他的方法,美国堪萨斯大学医学院分子生物学研究院副院长Shrikant Anant教授在Mol Cancer Ther上公开表示,巩长旸的方法“不使用有毒有机溶剂和剧烈条件,是高效、稳定、安全的”。
逐梦前行 挫折的背后是成长
2015年8月,中组部第二批“万人计划”青年拔尖人才名单公示,巩长旸身在其中。此时,他当然已不再是学生,而是生物治疗国家重点实验室/“2011计划”生物治疗协同创新中心副研究员、硕士生导师。而他的成长苗头,早在几年前就已经悄悄萌芽。
“刚到实验室的时候,我做的是一种新型的纳米材料制剂,温敏型水凝胶。”巩长旸介绍,这种水凝胶性能比较独特,可以感受到外界的一些刺激,并在温度或其他刺激条件下,做出相应的相变。“我们希望实现这样一个目标,当它在低温(室温)情况下是液体,便于注射或与药物复合制剂;一旦注射到体内的靶点,温度升高后,就转变为不可流动的固体,在原位缓释药物。”一言而概之,巩长旸是希望做出一种理想的适用于肿瘤局部治疗的新型水凝胶。一旦实现,该药物的临床前景必然不可限量。
然而,理想是丰满的,现实却很骨感。巩长旸和他的同伴们查阅了海量的文献,又一遍遍去做实验,初期做出来的总是与他们的设定相反。“我们看到的总是低温下是固体,升温后反倒成了液体。”用他的话说,那会儿,他们“想破脑袋”也做不出想要的性能。几个月下来,一群人都难免沮丧。
“经过了沮丧的这一两天,我想,一定是有哪些细微的环节没有注意到。”巩长旸提起精神,把之前所有的参数都拿过来,一项一项地去检查。之后的大半年里,他们的时间表单调枯燥:早上7点多到实验室,8点开始准备,9点正式实验,实验周期在3个小时左右,完成了就到了中午12点;半个小时的午饭后,再继续准备,下午1点钟进入下一个实验周期。因为样品要在冰箱中储存15个小时才能使用,他们通常在下午5点钟制备第二天上午的样品。晚饭后,继续在实验室学习文献、分析结果,晚上9点钟又开始制备第二天下午的样品。
时间一天天过去,参数一个个改变,他们终于把该有的性能做了出来。“真的只是在很小的地方出了问题,可是发现的过程很难。做完之后,回头再看,你会发现挫折和失败是最好的老师,它是你进步或成功的必经过程。”巩长旸感慨道。有了那场经历,他现在也总是对学生们说,“不要害怕失败,你越是觉得挫折痛苦的时候,越是你成长的时候。相反,你越是感觉安逸舒服的时候,其实你反而在退步了。”
温敏型水凝胶制备出来之后,巩长旸利用其包载紫杉醇、5-Fu等抗肿瘤药物,获得了可腹腔注射的新型原位缓释制剂,可显著提高腹腔化疗药物浓度和滞留时间,提高其抗肿瘤及抗腹腔转移效果;包载和厚朴酚,发现其对肺癌恶性胸腔积液有显著的治疗效果。其中,紫杉醇原位缓释凝胶制剂可以有效防治乳腺癌术后复发,载姜黄素温敏型水凝胶为解决大面积全皮缺损的修复奠定了基础。药物缓控释领域著名期刊J Control Release引用了巩长旸3篇关于温敏型水凝胶用于局部药物缓释的文章,并进行了正面评述:“水凝胶局部药物缓释体系减少了给药次数,有利于提高患者的依从性”。
巩长旸的温敏型水凝胶系列引起了一众关注。对他来说,更重要的还是“有用”。在研究中,他发现温度敏感型水凝胶有良好的防治术后腹腔组织粘连的作用,并创新地提出了水凝胶防治腹腔粘连的作用机理。
“术后组织粘连是指在外科手术中由于机械损伤、感染、射线或异物等原因造成组织创伤,使相邻的组织或者器官之间发生不正常的粘附,是普通盆腹腔手术后的常见疾病,发生率约为67%?93%。”如果这种水凝胶防粘连制剂能够进入临床,一定会为患者带来福音。
授业有道 感念师恩
四川大学浓厚的学习氛围以及它的包容与开放,吸引着无数学子,巩长旸也受益匪浅,尤其自魏于全院士身上。“小时候说立志要当一个科学家,其实只是一个很模糊的概念,并不知道这到底意味着什么。魏老师不仅是我研究生阶段的老师,也不仅是我工作上的领导,更是我的人生导师,从他身上,我学到了很多东西,也真正了解到什么是科研,怎么做好科研。”在接受采访时巩长旸回忆道。
一次,他们要做流式细胞术分析,由于染色比较多,几乎都是三色或四色,调整起来难度比较大。他们一直忙到晚上8点还没有头绪。魏于全院士刚好巡查到实验室,就进来和他们一起讨论问题在哪里。“他忙了一天也很累了,还是坐下来和我们一起调整,又指导我们做结果分析,等到全部完成,我们收拾好东西离开,已经是凌晨一点钟了。”
当巩长旸成为硕士生导师,他从魏于全院士身上所得到的感佩也被传递下去。“要做好事情,首先要做好人,这是最重要的一点。其次才是去培养他们的科研思维。”
从学生阶段走过,巩长旸明白,本科生的实验往往是照着老师的说法去做。“但真正的科研并不是这样的过程,需要科研人员发挥自己的主观能动性去创造才可以。”巩长旸对学生们说自己的经历,培养他们在遇到问题时,主动去分析问题、解决问题的能力。他的挫折教育,还包括要有强大的心理。“经受挫折之后,当然会有一些挫败感,但是一定要从中吸取教训,让它更加激励以后的工作,而非意志消沉下去。最后才是实验技巧、写作技巧等知识性的东西。”
并非说教,这也是他对自己的要求。先来看一组数据,目前,巩长旸已发表SCI学术论文86篇,引用1500余次,他引1200余次,h-index为24。其中,以第一、共同第一及通讯作者发表学术论文60篇(IF>5论文23篇);3篇论文入选ESI“高引用论文”。对一位刚刚度过35岁生日的青年学者来说,这个成绩确实不错。他却在得知入选青年拔尖人才之后说,“这是一个认可,也是一种促进,是一份沉甸甸的责任。无论怎样,我都是想做一个踏实勤奋的科研人,坚持初衷,做出真正有用的东西,不要迷失自己。”至于未来,他还希望能够去国外顶尖的实验室去参观学习,“看一下别人是怎么做科研的。”
虽然巩长旸迈入科研之旅的时间不算长,却也体会到科研人的“不一样”,“我们不可能完全把工作和生活完全分隔开。”
实验室会定期组织老师们去打羽毛球,巩长旸很喜欢参加,他更喜欢在打球时和不同学科的老师交流国际进展,说不定哪一个碰撞就引发了一串“火花”。
晚上下班,除了晚饭和短暂的交流,他更多时间都窝在书房里。“我在家里,但又好像不在。现在年岁渐长,父母也慢慢变老,还是要提高自己的工作效率,多陪陪家人。”
在他口中,有很多要感谢的人:魏于全院士、钱志勇教授、爱人、父母……“不管我取得什么成绩,都有他们的功劳。”
来源:科学中国人 2015年第11期
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