原位可注射pH/温度双响应载药水凝胶的制备及抗肿瘤应用  

In Situ Injectable Drug-loaded pH/Temperature Responsive Hydrogel with Application to Tumor Therapy

作　　者：蒋力 唐昭敏 赵健清 李世杰[1] 李昊宇 杨怡宁 潘皛 王新茗 JIANG Li;TANG Zhaomin;ZHAO Jianqing;LI Shijie;LI Haoyu;YANG Yining;PAN Xiao;WANG Xinming(School of New Energy and Materials,Southwest Petroleum University,Chengdu 610500,China;School of Pharmacy,Chengdu Medical College,Chengdu 610500,China;Department of Pharmacy,The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]西南石油大学新能源与材料学院,成都610500 [2]成都医学院药学院,成都610500 [3]成都医学院第一附属医院药学部,成都610500

出　　处：《材料导报》2025年第6期242-248,共7页Materials Reports

基　　金：国家自然科学基金(51803174);四川省科学基金项目(2024NSFSC0988);四川省玄武岩纤维复合材料开发及应用工程技术研究中心开放基金(2022SCXWYXWFC002)。

摘　　要：传统化疗在癌症治疗中取得了一定成功,但仍然存在非靶向治疗、副作用严重等缺陷,急需一种更精准、有效的治疗方法。本工作开发了一种可注射pH/温度双响应水凝胶。以季戊四醇(PETP)为引发剂、氯化亚锡(SnCl_(2))为催化剂,对ε-己内酯(ε-CL)进行开环聚合反应,合成四臂星型聚己内酯(4PCL)。利用4PCL与4-羧基苯甲醛(p-CBA)的酯化反应制备4PCL-CBA,再将4PCL-CBA、普朗尼克F127以及聚乙烯亚胺(PEI)水溶液按照一定比例混合,成功制得F127/PEI/4PCL-CBA(FECC)水凝胶。FECC水凝胶在37℃响应交联成胶,具有良好的可注射性。负载化疗药物阿霉素(DOX)的FECC水凝胶在肿瘤弱酸环境中168 h的DOX释放率为45.3%,释放平稳,无突释,而在模拟血液循环的中性环境中DOX累积释放率仅19.8%,表明DOX@FECC水凝胶实现了药物缓释。在细胞实验中,FECC水凝胶对正常血管内皮细胞(EC)无明显毒性,而DOX@FECC载药水凝胶能显著杀死人源乳腺癌细胞(4T1)。Conventional chemotherapy,though has achieved certain success in cancer treatment,still faces obvious shortcomings including non-specific therapy and serious side effects,intensifying the need for a more precise and effective alternation.In this study,an injectable pH and tem-perature dual-responsive hydrogel F127/PEI/4PCL-CBA(FECC)was developed.Using pentaerythritol(PETP)as the initiator and SnCl_(2) as the catalyst,four-armed star-shaped polycaprolactone(4PCL)was synthesized through the ring opening polymerization reaction ofε-caprolactone(ε-CL).Then the 4PCL was esterified with p-benzaldehyde carboxylic acid(p-CBA)to prepare 4PCL-CBA.And the FECC hydrogel was suc-cessfully prepared by mixing 4PCL-CBA,pluronic F127 and polyethyleneimine(PEI)aqueous solution in a certain proportion,which can be crosslinked at 37℃and has good injectability.The doxorubicin(DOX)-loaded FECC hydrogel exhibited a 168-hour DOX release rate of 45.3%with a stable and unhasty release phenomenon under a tumor-like weakly acidic condition,and a cumulative DOX release of only 19.8%in the neutral environment simulating blood circulation.This demonstrates the effective controlled release of the DOX@FECC hydrogel in vitro.In the cell experiment,FECC hydrogel displayed no obvious toxicity to normal vascular endothelial cells(EC),while DOX@FECC hydrogel could signi-ficantly kill the human breast cancer cells(4T1).

关 键 词：癌症治疗 原位水凝胶 PH响应 温度响应 可控释药 

分 类 号：TB39[一般工业技术—材料科学与工程]