鞏長旸,男,1980年9月出生,博士學位。四川大學華西醫院生物治療全國重點實驗室、“2011計劃”生物治療協同創新中心、生物治療轉化醫學國家重大科技基礎設施、國家“重大新藥創制”科技重大專項“國家創新藥物研發綜合大平臺”學術帶頭人,研究員,博士研究生導師。2018年國家自然科學基金優秀青年基金獲得者,入選2015年國家中組部“萬人計劃”青年拔尖人才支持計劃,獲2013年全國百篇優秀博士學位論文提名獎,2013年四川省百篇優秀博士學位論文,中國抗癌協會青年理事會理事,中國生物醫學工程學會納米醫學與工程學分會常務委員,中國抗癌協會納米腫瘤學分會委員,中國生物物理協會納米生物學分會委員會委員,中國生物材料學會納米生物材料分會第二屆委員會委員,中國病理生理學會免疫學專業委員會委員,中國生物物理協會材料生物學與智能診療技術分會委員,中國醫藥生物技術協會生物醫學成像技術分會第一屆委員會委員,四川省藥學會納米藥物專業委員會委員,第十三批四川省學術和技術帶頭人,第十三批四川省衛生健康委員會學術技術帶頭人,獲2021年四川省杰出青年科技人才項目。1999-2003年就讀于四川大學生物工程專業,獲理學學士學位。2005年在四川大學生物治療國家重點實驗室攻讀博士學位(碩博連讀),在著名腫瘤治療學家魏于全院士的指導下完成博士論文研究工作。2010年獲四川大學細胞生物學專業博士學位,同年7月起任四川大學華西醫院生物治療國家重點實驗室助理研究員、副研究員、研究員。主要研究領域為新型自組裝基因、疫苗和藥物遞送系統、醫用生物材料、納米生物技術、腫瘤治療。主持和參與國家自然科學基金優秀青年基金、面上項目、青年基金,科技部863重點項目“納米生物材料研發”,科技部重點研發計劃,科技部“重大新藥創制”科技重大專項,教育部博士點基金,四川省科技支撐計劃等多項國家及省部級基金項目。以第一發明人申報中國發明專利13項,其中13項已授權。現已發表SCI學術論文100余篇(所有工作均在國內完成),論文被引用XXX次,他引XXX次,h-index為33。其中,以通訊或第一作者在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)等國際雜志發表SCI論文100余篇(IF>10論文34篇,10>IF>5論文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等國際SCI學術期刊引用XXX次,他引XXX次。三篇論文(ACS Nano, 2017; Biomaterials, 2013; Int J Pharm, 2009)入選ESI“高被引用論文”。研究成果已經作為他人進一步研究的基礎, 并得到其他研究論文的證實。受Adv Drug Deliver Rev (IF 17.873), Nano Res (IF 10.262)等期刊邀請撰寫特邀綜述6篇。并受美國Nova出版社之邀,參與編寫英文書 “Polymer Aging, Stabilizers and Amphiphilic Block Copolymers”. Editors: Liudvikas Segewicz and Marijus Petrowsky. Nova Publishers. 2011-1st Quarter.(ISBN: 978-1-60692-928-5)。由于相關領域研究工作受到國際重視,受主編之邀,任Chinese Chem Lett (IF 8.455), BioMed Res Int (IF 3.246)等學術期刊編委。為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余種國際期刊審特邀稿人。
教育及工作經歷:
2003年畢業于四川大學,獲學士學位。
2010年于四川大學獲博士學位。
2010年起在四川大學華西醫院生物治療國家重點實驗室進行科研工作。
學術兼職:
1. 任職名稱:中國抗癌協會;職務:青年理事會理事;首任時間:2019年2月15日;屆數:第一屆,第二屆;任期年限:2019年2月15日至2027年7月14日。
2. 任職名稱:中國生物醫學工程學會納米醫學與工程學分會;職務:常務委員;首任時間:2023年5月20日;屆數:第二屆;任期年限:2023年5月至2027年5月。
3. 任職名稱:中國生物材料學會納米生物材料分會;職務:委員會委員;首任時間:2019年10月;屆數:第二屆、第三屆;任期年限:2019年10月至2027年10月。
4. 任職名稱:中國生物物理協會納米生物學分會;職務:委員會委員;首任時間:2021年8月;屆數:第五屆;任期年限:2021年8月至2025年8月。
5. 任職名稱:中國抗癌協會納米腫瘤學分會;職務:委員會委員;首任時間:2021年10月;屆數:第三屆;任期年限:2021年10月至2025年10月。
6. 任職名稱:中國病理生理學會免疫學專業委員會;職務:委員;首任時間:2018年11月15日;屆數:第八屆、第九屆;任期年限:2018年11月15日至今(第九屆是2020年開始,好像六年一屆)。
7. 任職名稱:中國生物物理學會材料生物學與智能診療技術分會;職務:委員;首任時間:2021年8月;屆數:第X屆;任期年限:2021年8月至2025年8月。
8. 任職名稱:中國醫藥生物技術協會生物醫學成像技術分會;職務:委員會委員;首任時間:2019年10月;屆數:第一屆、第二屆;任期年限:2023年11月至2027年10月。
9. 任職名稱:中國生物醫學工程學會納米醫學與工程學分會;職務:青年委員會委員;首任時間:2019年4月20日;屆數:第二屆;任期年限:2019年4月20日至2023年4月19日。
10. 任職名稱:中國生物物理協會納米生物學分會;職務:青年委員會委員;首任時間:2019年4月;屆數:第五屆;任期年限:2019年4月至2021年8月。
11. 任職名稱:中國抗癌協會納米腫瘤學分會;職務:青年委員會委員;首任時間:2018年8月6日;屆數:第一屆;任期年限:2018年8月6日至2022年8月5日。
12. 任職名稱:四川省藥學會納米藥物專委會;職務:委員;首任時間:2023年4月;屆數:第一屆;任期年限:2023年4月至2026年12月。
13. 任職名稱:四川大學華西第二醫院婦幼藥物研究與轉化實驗室學術委員會;職務:委員;首任時間:2023年9月;屆數:第一屆;任期年限:2023年9月至2026年12月。
期刊任職:
1. 任職名稱:Acta Pharmaceutica Sinica B(SCI,IF 14.5);職務:青年編委;首任時間:2023年9月;屆數:第三屆;任期年限:2023年9月至今。
2. 任職名稱:Chinese Chemical Letters(SCI,IF 9.1);職務:青年編委;首任時間:2018年5月;屆數:第二屆、第三屆,第四屆;任期年限:2018年5月至2022年6月。
3. 任職名稱:BioMed Research International(SCI,IF 2.276);職務:編委;首任時間:2013年3月;屆數:第一屆;任期年限:2013年3月至今。
4. 任職名稱:International Scholarly Research Notices;職務:編委;任期年限:2014年5月至2017年7月。
5. 任職名稱:Advances in Pharmaceutics;職務:編委;任期年限:2013年5月至2016年8月。
6. 任職名稱:藥學學報;職務:青年編委;首任時間:2023年9月;屆數:第三屆;任期年限:2023年9月至2022年6月。
7. 任職名稱:四川大學學報(醫學版);職務:青年編委;首任時間:2023年3月;屆數:第六屆;任期年限:2023年5月至2025年4月。
主講課程:
資料更新中……
培養研究生情況:
資料更新中……
招生情況:
歡迎藥學、生命科學、基礎及臨床醫學、化學或其他相關專業背景的同學報考,樂意接受推免生。
研究方向:
1. 新型靶向基因傳遞系統。
2. 新型靶向藥物傳遞系統。
3. 多糖類藥物。
4. 細胞表面功能化修飾。
5. 醫用高分子材料等研究工作。
承擔科研項目情況:
負責和參與多項國家和省部級科研項目,包括國家科技部863項目,“重大新藥創制”國家重大專項,國家自然科學基金,四川省科技支撐計劃,教育部博士點基金,四川大學優秀青年學者基金等。
2011年1月,科技部“重大新藥創制”科技重大專項,“新型多烯紫杉醇水性制劑研發”第一主研人員。
科研成果:
1. 發現PEG/PCL膠束是一種較理想的納米藥物傳遞系統,并以此為“跳板”做了一系列出擊。針對臨床紫杉醇注射液中聚氧乙烯蓖麻油易引起過敏反應的問題,他采用PEG/PCL納米膠束包載紫杉醇和多烯紫杉醇,獲得了可靜脈注射的新型紫杉烷納米緩釋制劑顯著提高其抗腫瘤效果并降低毒副作用,為創制新型紫杉烷水基制劑提供了新選擇。
2. 姜黃素也具有疏水性,先是通過PEG/PCL納米膠束單獨包載姜黃素,制備出一種新型姜黃素納米緩釋制劑,為腫瘤轉移的治療提供了新思路,又開始考慮把姜黃素與其他藥物作為一個共同體包載在PEG/PCL納米膠束中。比如,與親水性的阿霉素一起,可以在親—疏水藥物之間產生協同作用,顯著提高腫瘤細胞對阿霉素的攝取;而與紫杉醇結合,可以在體內外顯著提高紫杉醇的抗腫瘤效果,摒除紫杉醇耐藥性的缺點。美國堪薩斯大學醫學院分子生物學研究院副院長Shrikant Anant教授在Mol Cancer Ther上公開表示,鞏長旸的方法“不使用有毒有機溶劑和劇烈條件,是高效、穩定、安全的”。
3. 溫敏型水凝膠制備出來之后,鞏長旸利用其包載紫杉醇、5-Fu等抗腫瘤藥物,獲得了可腹腔注射的新型原位緩釋制劑,可顯著提高腹腔化療藥物濃度和滯留時間,提高其抗腫瘤及抗腹腔轉移效果;包載和厚樸酚,發現其對肺癌惡性胸腔積液有顯著的治療效果。其中,紫杉醇原位緩釋凝膠制劑可以有效防治乳腺癌術后復發,載姜黃素溫敏型水凝膠為解決大面積全皮缺損的修復奠定了基礎。藥物緩控釋領域著名期刊J Control Release引用了鞏長旸3篇關于溫敏型水凝膠用于局部藥物緩釋的文章,并進行了正面評述:“水凝膠局部藥物緩釋體系減少了給藥次數,有利于提高患者的依從性”。
4. 在研究中,發現溫度敏感型水凝膠有良好的防治術后腹腔組織粘連的作用,并創新地提出了水凝膠防治腹腔粘連的作用機理。
發明公開:
[1]鞏長旸, 梁秀琪, 吳秦潔. 一種智能響應型可注射水凝膠及其制備方法和應用[P]. 四川省: CN116763725A, 2023-09-19.
[2]鞏長旸, 楊茜, 高玲, 鄭嶺楠, 魏院鋒. 一種具有佐劑效應的水凝膠及其制備方法和用途[P]. 四川省: CN116688114A, 2023-09-05.
[3]鞏長旸, 宋林江, 吳秦潔, 魏于全. 一種腫瘤靶向多功能非病毒基因載體及其制備方法和用途[P]. 四川省: CN113318242A, 2021-08-31.
[4]鞏長旸, 吳秦潔, 王寧. 一種多功能外殼材料PMTPH及其制備方法和用途[P]. 四川省: CN112386711A, 2021-02-23.
[5]鞏長旸, 吳秦潔, 王寧. 一種精氨酸修飾的聚乙烯亞胺及其制備方法和用途[P]. 四川省: CN112210077A, 2021-01-12.
[6]鞏長旸, 羅晗, 楊茜, 朱精強, 李志輝, 唐懷榮. 一種包含膠束的可注射復合水凝膠雙載藥系統的制備方法[P]. 四川省: CN112156066A, 2021-01-01.
[7]鞏長旸, 羅晗, 楊茜, 朱精強, 李志輝, 唐懷榮. 一種共載紫杉烷類膠束和鉑類藥物的可注射水凝膠及其制備方法和用途[P]. 四川省: CN112089729A, 2020-12-18.
[8]鞏長旸, 吳秦潔, 王寧. 一種氨基酸修飾的聚乙烯亞胺化合物及其制備方法和用途[P]. 四川省: CN112094409A, 2020-12-18.
[9]鞏長旸, 周長庚. 一種含硼納米靶向藥物的制備方法[P]. 四川省: CN111281975A, 2020-06-16.
[10]鞏長旸, 吳秦潔, 何濤, 魏于全. 一種免疫佐劑及其制備方法[P]. 四川省: CN109694484A, 2019-04-30.
[11]鞏長旸, 吳秦潔, 王寧. 寡聚透明質酸或其鹽在制備治療心肌梗死的藥物中的用途[P]. 四川省: CN109528753A, 2019-03-29.
[12]蔡璐璐, 鞏長旸, 童榮生, 王強, 余繼英, 王巖. 一種抗癌天然產物藤黃酸的納米制劑及其制備方法[P]. 四川: CN108619094A, 2018-10-09.
[13]鞏長旸, 謝永美, 曾安琪, 楊超, 宋林江, 魏于全. 一種pH敏感型的SN#38膠束及其制備方法和用途[P]. 四川: CN106963731A, 2017-07-21.
[14]鞏長旸, 吳秦潔, 宋林江, 魏于全. 一種用于基因傳遞的非病毒基因載體及其制備方法和用途[P]. 四川: CN106755027A, 2017-05-31.
[15]鞏長旸, 吳秦浩, 魏于全, 李玲. 一種修飾的聚乙烯亞胺化合物及其制備方法和應用[P]. 四川: CN106188537A, 2016-12-07.
[16]鞏長旸, 丁健, 劉新宇, 吳秦潔, 魏于全, 李玲. N,O-羧甲基化殼聚糖-多醛基透明質酸凝膠及其用途[P]. 四川: CN103897206A, 2014-07-02.
[17]錢志勇, 鞏長旸, 魏于全, 趙霞. 包載化療藥物的聚合物水凝膠及其在預防腫瘤復發和防治術后腹腔粘連中的用途[P]. 四川: CN102973941A, 2013-03-20.
[18]錢志勇, 魏于全, 趙霞, 鞏長旸. PCL-PEG-PCL三嵌段共聚物在制備醫用防粘連材料中的用途[P]. 四川: CN101837006A, 2010-09-22.
發明授權:
[1]鞏長旸, 梁秀琪, 吳秦潔. 一種智能響應型可注射水凝膠及其制備方法和應用[P]. 四川省: CN116763725B, 2023-11-24.
[2]鞏長旸, 吳秦潔, 王寧. 一種氨基酸修飾的聚乙烯亞胺化合物及其制備方法和用途[P]. 四川省: CN112094409B, 2023-08-08.
[3]鞏長旸, 吳秦潔, 王寧. 一種精氨酸修飾的聚乙烯亞胺及其制備方法和用途[P]. 四川省: CN112210077B, 2023-07-04.
[4]鞏長旸, 宋林江, 吳秦潔, 魏于全. 一種腫瘤靶向多功能非病毒基因載體及其制備方法和用途[P]. 四川省: CN113318242B, 2023-03-10.
[5]鞏長旸, 周長庚. 一種含硼納米靶向藥物的制備方法[P]. 四川省: CN111281975B, 2023-02-24.
[6]鞏長旸, 羅晗, 楊茜, 朱精強, 李志輝, 唐懷蓉. 一種共載紫杉烷類膠束和鉑類藥物的可注射水凝膠及其制備方法和用途[P]. 四川省: CN112089729B, 2022-04-01.
[7]鞏長旸, 吳秦潔, 王寧. 一種多功能外殼材料PMTPH及其制備方法和用途[P]. 四川省: CN112386711B, 2022-02-22.
[8]鞏長旸, 吳秦潔, 何濤, 魏于全. 一種免疫佐劑及其制備方法[P]. 四川省: CN109694484B, 2021-08-27.
[9]鞏長旸, 羅晗, 楊茜, 朱精強, 李志輝, 唐懷榮. 一種包含膠束的可注射復合水凝膠雙載藥系統的制備方法[P]. 四川省: CN112156066B, 2021-08-17.
[10]鞏長旸, 吳秦潔, 王寧. 寡聚透明質酸或其鹽在制備治療心肌梗死的藥物中的用途[P]. 四川省: CN109528753B, 2021-01-22.
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實用新型:
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現已發表SCI學術論文100余篇(所有工作均在國內完成),論文被引用XXX次,他引XXX次,h-index為33。其中,以通訊或第一作者在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)等國際雜志發表SCI論文100余篇(IF>10論文34篇,10>IF>5論文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等國際SCI學術期刊引用XXX次,他引XXX次。。
參與編寫英文專著:
[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)
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[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
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[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
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[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
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[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#(co-first author); Dong, Peng Wei; Shi, Shuai; Fu, Shao Zhi; Guo, Gang; Hu, Huo Zhen; Zhao, Xia; Wei, Yu Quan; Qian, Zhi Yong*(Corresponding author).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#(co-first author); Shi, Shuai; Fu, Shao Zhi; Yang, Jin Liang; Guo, Gang; Zhao, Xia; Wei, Yu Quan; Qian, Zhi Yong*(Corresponding author).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. IF= 3.784
[114]Gong, ChangYang; Shi, Shuai; Wang, XiuHong; Wang, YuJun; Fu, ShaoZhi; Dong, PengWei; Chen, LiJuan; Zhao, Xia; Wei, YuQuan; Qian, ZhiYong*(Corresponding author).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. IF= 3.466
[115]Gong, Chang Yang; Fu, Shao Zhi#(co-first author); Gu, Ying Chun#(co-first author); Liu, Cai Bing; Kan, Bing; Deng, Hong Xin; Luo, Feng; Qian, Zhi Yong*(Corresponding author).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. IF= 3.057
[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*(Corresponding author); Wei, Yu Quan; Qian, Zhi Yong*(Corresponding author).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. IF= 3.329
[118]Gong, ChangYang; Shi, Shuai#(co-first author); Dong, PengWei; Kan, Bing; Gou, MaLing; Wang, XianHuo; Li, XingYi; Luo, Feng; Zhao, Xia; Wei, YuQuan; Qian, ZhiYong*(Corresponding author).Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel.International Journal of Pharmaceutics, 2009, 365(1-2): 89-99. IF= 6.51
[119]Liu, Cai Bing; Gong, Chang Yang#(co-first author); Huang, Mei Juan#(co-first author); 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#,*(co-first author, Corresponding author).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.IF= 3.405
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代表性中文論文:
[1]鞏長旸, 顧迎春, 謝震, 謝希惠, 劉彩兵, 闞兵, 涂銘旌, 魏于全, 錢志勇. 一種可生物降解溫度敏感型聚乙二醇-聚己內酯-聚乙二醇水凝膠的合成和表征[J]. 生物醫學工程學雜志, 2008, (05): 1121-1125.
[2]鞏長旸, 顧迎春, 劉彩兵, 闞兵, 茍馬玲, 鄧洪新, 涂銘旌, 魏于全, 錢志勇. 溫度敏感型PCL-Pluronic-PCL水凝膠的合成與性能[J]. 高分子材料科學與工程, 2007, (04): 86-88+93.
[3]茍馬玲, 謝震, 王輝, 鞏長旸, 涂銘旌, 錢志勇. 采用化學共沉淀法制備納米磁流體[J]. 華西醫學, 2007, (02): 343-344.
[4]賴慶柯,張永奎,梁斌,鞏長旸. 酸性Fe(Ⅲ)溶液催化氧化S(Ⅳ)的研究[J]. 環境科學學報, 2004, (06): 1091-1097.
榮譽獎勵:
1. 2013年,獲全國百篇優秀博士生論文提名獎。
2. 2012年,獲四川省百篇優秀博士生論文。
3. 2015年,入選中組部第二批“萬人計劃”青年拔尖人才。
4. 3篇論文入選ESI“高引用論文”。
——記四川大學生物治療國家重點實驗室鞏長旸博士
“20世紀初,癌癥的治愈率一直為零;二三十年代,隨著外科手術治療的誕生,癌癥的存活率達到了25%;60年代,放療和化療的使用讓癌癥的治愈率上升到了38%;80年代,隨著技術的進步,該數據又上升到了46%。綜合這些治療手段,目前癌癥的存活率約為50%。這也預示著研發新的治療手段迫在眉睫,生物治療在這樣的環境下應運而生。”2015(第五屆)抗體藥物及新藥研發高峰會上,魏于全院士在主題演講中說道。
生物治療的靶向性,使其具有有的放矢的功效,順應了個性化醫療和精準醫療的發展趨勢。受到導師魏于全院士的影響,鞏長旸也走上了生物治療研究之路,他瞄準的重點是新型藥物和基因傳遞系統。
年少立志 做有用的研究
“神奇”,在談到對自己專業的初印象時,鞏長旸用了這樣一個詞。
新型藥物和基因傳遞系統,是近二三十年新興起的一個研究領域。不同于傳統的研究方向和學科方向,它是以藥學、納米技術、醫學和生物材料學等學科交叉融合催生的“新人”。
“我感覺它是基礎研究與應用研究并重的學科,也是現在生物醫藥領域研究的前沿和熱點。”鞏長旸說,“借助這個方向,我們可以將廣泛的藥物,包括小分子藥物、基因、蛋白等精確地導入到腫瘤或其他病灶部位,盡量減少在身體其他器官的分布,使治療發揮出更好的療效,并且降低藥物的系統毒性。”
能發揮這樣的功效,在剛進入四川大學華西醫院生物治療國家重點實驗室攻讀碩士學位的鞏長旸眼中,“神奇”二字并不夸張。那是2005年,鞏長旸25歲,師從我國著名腫瘤治療學家魏于全院士。
古人說山中無日月,對年輕的鞏長旸來說,鉆進一個新的世界,時間也很容易被忘卻。2007年,他提前取得了攻讀博士學位的資格,深受魏于全院士賞識。2008年,科技部“863”重點項目納米生物材料研發正式啟動,魏于全院士也將他帶入項目中。以學生身份參與這么重要的項目,和那些學術上的大咖們一起工作,鞏長旸很滿足。“也是在那時候,我了解到什么是國家重大項目、重要需求”,他忍不住重復魏于全院士當年常對他說的那句話,“我們做科研,一定要按照國家的重大需求去解決實際問題,才能真正做出有用、有意義的東西。”
“生物和醫學,是我從小就一直喜歡的方向。”1999年,19歲的鞏長旸從沈陽來到成都。生活令人成長,正當他專心在四川大學學習生物工程專業知識的時候,一個噩耗傳來——他的奶奶因為惡性腫瘤離開了。悲慟過后,鞏長旸開始關心腫瘤治療的相關信息,想要再通過自己的努力,真正在腫瘤領域做些有用的事。魏于全院士的話,戳中了他心中最柔軟的地方,引起了他深刻的共鳴。從此,這句話成為他科研之旅中重要的指向標,再未動搖過。
來到生物治療國家重點實驗室后,鞏長旸最先做的就是去了解這個實驗室的研究動態。他發現,在新型的生物治療手段上,無論是基因治療、免疫治療,還是小分子靶向藥物治療,都需要一些合適的載體,才能發揮出更好的療效。“一是安全,二是有效”,鞏長旸肯定地給出研究的兩大重要前提。
2011年1月,科技部“重大新藥創制”科技重大專項啟動。這一次,鞏長旸以項目組副組長的身份出現,成為“新型多烯紫杉醇水性制劑研發”的第一主研人員。
“為什么會有這方面的研究?因為現在很多科研機構和制藥公司研制出的活性分子,不能直接應用于人體,必須經過一個制劑的過程,這個過程很困難。比如,很多活性分子雖然在體外有很好的藥效,但由于疏水性強,很難形成均勻水基制劑,嚴重限制了其成藥性。再比如現在腫瘤治療中常用的一線藥物紫杉醇,它本身是一種疏水性藥物,為了制劑,會采用將聚氧乙烯蓖麻油和酒精1:1的混合液,這其實存在很大的安全隱患。”提起這些,鞏長旸憂心忡忡,“聚氧乙烯蓖麻油會引起人的超敏反應,臨床中會先給患者注射地塞米松等來預防過敏,但也增加了臨床工作,應用起來不方便。”
鞏長旸的研究就是為了解決這些問題。經過反復實驗,他發現PEG/PCL膠束是一種較理想的納米藥物傳遞系統,并以此為“跳板”做了一系列出擊。針對臨床紫杉醇注射液中聚氧乙烯蓖麻油易引起過敏反應的問題,他采用PEG/PCL納米膠束包載紫杉醇和多烯紫杉醇,獲得了可靜脈注射的新型紫杉烷納米緩釋制劑顯著提高其抗腫瘤效果并降低毒副作用,為創制新型紫杉烷水基制劑提供了新選擇。
在隨后的研究中,他打起了姜黃素的主意。姜黃素也具有疏水性,他先是通過PEG/PCL納米膠束單獨包載姜黃素,制備出一種新型姜黃素納米緩釋制劑,為腫瘤轉移的治療提供了新思路,又開始考慮把姜黃素與其他藥物作為一個共同體包載在PEG/PCL納米膠束中。比如,與親水性的阿霉素一起,可以在親—疏水藥物之間產生協同作用,顯著提高腫瘤細胞對阿霉素的攝取;而與紫杉醇結合,可以在體內外顯著提高紫杉醇的抗腫瘤效果,摒除紫杉醇耐藥性的缺點。
“我們在前期制備過程中盡量不使用加高熱、高速攪拌等劇烈的過程,也不使用有毒的有機溶劑,如果這些制劑要進行后期開發,就在最大程度上保障了安全性。看起來只是很小的工藝改進,我們也花了很大精力去探索。”鞏長旸補充道。國際同行們顯然也很認可他的方法,美國堪薩斯大學醫學院分子生物學研究院副院長Shrikant Anant教授在Mol Cancer Ther上公開表示,鞏長旸的方法“不使用有毒有機溶劑和劇烈條件,是高效、穩定、安全的”。
逐夢前行 挫折的背后是成長
2015年8月,中組部第二批“萬人計劃”青年拔尖人才名單公示,鞏長旸身在其中。此時,他當然已不再是學生,而是生物治療國家重點實驗室/“2011計劃”生物治療協同創新中心副研究員、碩士生導師。而他的成長苗頭,早在幾年前就已經悄悄萌芽。
“剛到實驗室的時候,我做的是一種新型的納米材料制劑,溫敏型水凝膠。”鞏長旸介紹,這種水凝膠性能比較獨特,可以感受到外界的一些刺激,并在溫度或其他刺激條件下,做出相應的相變。“我們希望實現這樣一個目標,當它在低溫(室溫)情況下是液體,便于注射或與藥物復合制劑;一旦注射到體內的靶點,溫度升高后,就轉變為不可流動的固體,在原位緩釋藥物。”一言而概之,鞏長旸是希望做出一種理想的適用于腫瘤局部治療的新型水凝膠。一旦實現,該藥物的臨床前景必然不可限量。
然而,理想是豐滿的,現實卻很骨感。鞏長旸和他的同伴們查閱了海量的文獻,又一遍遍去做實驗,初期做出來的總是與他們的設定相反。“我們看到的總是低溫下是固體,升溫后反倒成了液體。”用他的話說,那會兒,他們“想破腦袋”也做不出想要的性能。幾個月下來,一群人都難免沮喪。
“經過了沮喪的這一兩天,我想,一定是有哪些細微的環節沒有注意到。”鞏長旸提起精神,把之前所有的參數都拿過來,一項一項地去檢查。之后的大半年里,他們的時間表單調枯燥:早上7點多到實驗室,8點開始準備,9點正式實驗,實驗周期在3個小時左右,完成了就到了中午12點;半個小時的午飯后,再繼續準備,下午1點鐘進入下一個實驗周期。因為樣品要在冰箱中儲存15個小時才能使用,他們通常在下午5點鐘制備第二天上午的樣品。晚飯后,繼續在實驗室學習文獻、分析結果,晚上9點鐘又開始制備第二天下午的樣品。
時間一天天過去,參數一個個改變,他們終于把該有的性能做了出來。“真的只是在很小的地方出了問題,可是發現的過程很難。做完之后,回頭再看,你會發現挫折和失敗是最好的老師,它是你進步或成功的必經過程。”鞏長旸感慨道。有了那場經歷,他現在也總是對學生們說,“不要害怕失敗,你越是覺得挫折痛苦的時候,越是你成長的時候。相反,你越是感覺安逸舒服的時候,其實你反而在退步了。”
溫敏型水凝膠制備出來之后,鞏長旸利用其包載紫杉醇、5-Fu等抗腫瘤藥物,獲得了可腹腔注射的新型原位緩釋制劑,可顯著提高腹腔化療藥物濃度和滯留時間,提高其抗腫瘤及抗腹腔轉移效果;包載和厚樸酚,發現其對肺癌惡性胸腔積液有顯著的治療效果。其中,紫杉醇原位緩釋凝膠制劑可以有效防治乳腺癌術后復發,載姜黃素溫敏型水凝膠為解決大面積全皮缺損的修復奠定了基礎。藥物緩控釋領域著名期刊J Control Release引用了鞏長旸3篇關于溫敏型水凝膠用于局部藥物緩釋的文章,并進行了正面評述:“水凝膠局部藥物緩釋體系減少了給藥次數,有利于提高患者的依從性”。
鞏長旸的溫敏型水凝膠系列引起了一眾關注。對他來說,更重要的還是“有用”。在研究中,他發現溫度敏感型水凝膠有良好的防治術后腹腔組織粘連的作用,并創新地提出了水凝膠防治腹腔粘連的作用機理。
“術后組織粘連是指在外科手術中由于機械損傷、感染、射線或異物等原因造成組織創傷,使相鄰的組織或者器官之間發生不正常的粘附,是普通盆腹腔手術后的常見疾病,發生率約為67%?93%。”如果這種水凝膠防粘連制劑能夠進入臨床,一定會為患者帶來福音。
授業有道 感念師恩
四川大學濃厚的學習氛圍以及它的包容與開放,吸引著無數學子,鞏長旸也受益匪淺,尤其自魏于全院士身上。“小時候說立志要當一個科學家,其實只是一個很模糊的概念,并不知道這到底意味著什么。魏老師不僅是我研究生階段的老師,也不僅是我工作上的領導,更是我的人生導師,從他身上,我學到了很多東西,也真正了解到什么是科研,怎么做好科研。”在接受采訪時鞏長旸回憶道。
一次,他們要做流式細胞術分析,由于染色比較多,幾乎都是三色或四色,調整起來難度比較大。他們一直忙到晚上8點還沒有頭緒。魏于全院士剛好巡查到實驗室,就進來和他們一起討論問題在哪里。“他忙了一天也很累了,還是坐下來和我們一起調整,又指導我們做結果分析,等到全部完成,我們收拾好東西離開,已經是凌晨一點鐘了。”
當鞏長旸成為碩士生導師,他從魏于全院士身上所得到的感佩也被傳遞下去。“要做好事情,首先要做好人,這是最重要的一點。其次才是去培養他們的科研思維。”
從學生階段走過,鞏長旸明白,本科生的實驗往往是照著老師的說法去做。“但真正的科研并不是這樣的過程,需要科研人員發揮自己的主觀能動性去創造才可以。”鞏長旸對學生們說自己的經歷,培養他們在遇到問題時,主動去分析問題、解決問題的能力。他的挫折教育,還包括要有強大的心理。“經受挫折之后,當然會有一些挫敗感,但是一定要從中吸取教訓,讓它更加激勵以后的工作,而非意志消沉下去。最后才是實驗技巧、寫作技巧等知識性的東西。”
并非說教,這也是他對自己的要求。先來看一組數據,目前,鞏長旸已發表SCI學術論文86篇,引用1500余次,他引1200余次,h-index為24。其中,以第一、共同第一及通訊作者發表學術論文60篇(IF>5論文23篇);3篇論文入選ESI“高引用論文”。對一位剛剛度過35歲生日的青年學者來說,這個成績確實不錯。他卻在得知入選青年拔尖人才之后說,“這是一個認可,也是一種促進,是一份沉甸甸的責任。無論怎樣,我都是想做一個踏實勤奮的科研人,堅持初衷,做出真正有用的東西,不要迷失自己。”至于未來,他還希望能夠去國外頂尖的實驗室去參觀學習,“看一下別人是怎么做科研的。”
雖然鞏長旸邁入科研之旅的時間不算長,卻也體會到科研人的“不一樣”,“我們不可能完全把工作和生活完全分隔開。”
實驗室會定期組織老師們去打羽毛球,鞏長旸很喜歡參加,他更喜歡在打球時和不同學科的老師交流國際進展,說不定哪一個碰撞就引發了一串“火花”。
晚上下班,除了晚飯和短暫的交流,他更多時間都窩在書房里。“我在家里,但又好像不在。現在年歲漸長,父母也慢慢變老,還是要提高自己的工作效率,多陪陪家人。”
在他口中,有很多要感謝的人:魏于全院士、錢志勇教授、愛人、父母……“不管我取得什么成績,都有他們的功勞。”
來源:科學中國人 2015年第11期
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