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

doi:10.11896/cldb.24010129

材料导报

2025, Vol. 39

Issue (6): 24010129-7 https://doi.org/10.11896/cldb.24010129

高分子与聚合物基复合材料

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

蒋力¹, 唐昭敏^1,*, 赵健清¹, 李世杰¹, 李昊宇¹, 杨怡宁¹, 潘皛², 王新茗^3,*

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

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

JIANG Li¹, TANG Zhaomin^1,*, ZHAO Jianqing¹, LI Shijie¹, LI Haoyu¹, YANG Yining¹, PAN Xiao², WANG Xinming^3,*

1 School of New Energy and Materials, Southwest Petroleum University, Chengdu 610500, China
2 School of Pharmacy, Chengdu Medical College, Chengdu 610500, China
3 Department of Pharmacy, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China

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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(SnCl₂)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)。

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	蒋力
	唐昭敏
	赵健清
	李世杰
	李昊宇
	杨怡宁
	潘皛
	王新茗

关键词: 癌症治疗原位水凝胶 pH响应温度响应可控释药

Abstract: 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 temperature dual-responsive hydrogel F127/PEI/4PCL-CBA (FECC) was developed. Using pentaerythritol (PETP) as the initiator and SnCl₂ as the catalyst, four-armed star-shaped polycaprolactone (4PCL) was synthesized through the ring opening polymerization reaction of ε-caprolactone (ε-CL). Then the 4PCL was esterified with p-benzaldehyde carboxylic acid (p-CBA) to prepare 4PCL-CBA. And the FECC hydrogel was successfully 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).

Key words: cancer treatment in situ hydrogel pH response temperature response controlled drug release

出版日期: 2025-03-25 发布日期: 2025-03-24

ZTFLH:

TB39

基金资助: 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)

通讯作者: *唐昭敏,西南石油大学新能源与材料学院高级实验师、博士、硕士研究生导师。主要从事新型功能纳米材料在抗肿瘤方面的研究。
王新茗,成都医学院第一附属医院主管药师,硕士研究生。主要从事临床药学、数据挖掘方面的工作。tl8687@163.com;wangxinming@cmc.edu.cn

作者简介: 蒋力,西南石油大学新能源与材料学院硕士研究生,主要研究领域为新型功能纳米材料。

引用本文:

蒋力, 唐昭敏, 赵健清, 李世杰, 李昊宇, 杨怡宁, 潘皛, 王新茗. 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[J]. 材料导报, 2025, 39(6): 24010129-7.
JIANG Li, TANG Zhaomin, ZHAO Jianqing, LI Shijie, LI Haoyu, YANG Yining, PAN Xiao, WANG Xinming. In Situ Injectable Drug-loaded pH/Temperature Responsive Hydrogel with Application to Tumor Therapy. Materials Reports, 2025, 39(6): 24010129-7.

链接本文:

https://www.mater-rep.com/CN/10.11896/cldb.24010129 或 https://www.mater-rep.com/CN/Y2025/V39/I6/24010129

1 Ansa B E, Aldema-Mensah E, Sheats J Q, et al. AJPM Focus, 2023, 2(4), 100121.
2 Stabellini N, Cao L, Towe, C W, et al. Cancer Medicine, DOI:10. 1002/cam4. 6584.
3 Ozawa Y, Hicks K C, Minnar C M, et al. Oncoimmunology, 2021, 10(1), 1915561.
4 Hendriks L, Besse B. Nature, 2018, 558(7710), 376.
5 Danhier F, Feron O, Preat V. Journal of Controlled Release, 2010, 148(2), 135.
6 Tang Z M, Tian W J. Materials Reports, 2022, 36(3), 21120187 (in Chinese).
唐昭敏, 田维君. 材料导报, 2022, 36(3), 21120187.
7 Schmid P, Cortes J, Dent R, et al. New England Journal of Medicine, 2022, 386(6), 556.
8 Zhu Y, Zhu X, Tang C, et al. Biochimica et Biophysica Acta-Reviews on Cancer, 2021, 1876(2), 188593.
9 Spanogiannopoulos P, Kyaw T S, Guthrie B G H, et al. Nature Micro-biology, 2022, 7(10), 1605.
10 Hammerl D, Martens J W M, Timmermans M, et al. Nature Communications, 2021, 12(1), 5668.
11 Szczerba B M, Castro-Giner F, Vetter M, et al. Nature, 2019, 566(7745), 553.
12 Norouzi M, Nazari B, Miller D W. Drug Discovery Today, 2016, 21(11), 1835.
13 Zhao X, Chen X, Yuk H, et al. Chemical Reviews, 2021, 121(8), 4309.
14 Oliva N, Conde J, Wang K, et al. Accounts of Chemical Research, 2017, 50(4), 669.
15 Onaciu A, Munteanu R A, Moldovan A I, et al. Pharmaceutics, 2019, 11(9), 432.
16 Cai L, Liu S, Guo J, et al. Acta Biomaterial, 2020, 113, 84.
17 Raucci M G, D'Amora U, Ronca A, et al. Advanced Healthcare Material, 2020, 9(13), e2000349.
18 Maeda H, Tsukigawa K, Fang J. Microcirculation, 2016, 23(3), 173.
19 Bu Y, Zhang L, Liu J, et al. ACS Applied Material & Interfaces, 2016, 8(20), 12674.
20 Zhou W, Duan Z, Zhao J, et al. Bioactive Material, 2022, 17, 1.
21 Lee S Y, Yang M, Seo J H, et al. ACS Applied Material & Interfaces, 2021, 13(2), 2189.
22 Hopkins C C, de Bruyn J R. Journal of Rheology,2019, 63(1), 191.
23 Zhao R, Wang D, Xie J, et al. Chemical Engineering Journal,2022, 427, 131618.
24 Ding X, Li G, Xiao C, Liu Y, et al. Chemistry and Physics,2019, 220(3), 19000484.
25 Sarkar S, Bera S, Moitra P, et al. Materials Today Chemistry, 2023, 30, 101554.
26 Sun R, Chen Y, Yang Q, et al. International Journal of Pharmaceutics, 2022, 613, 121390.
27 Su M, Zhu Y, Chen J, et al. Chemical Engineering Journal, 2022, 435, 134926.
28 Liu G, Wang L, He Y, et al. Advanced Healthcare Materials, 2021, 10(23), 2101476.
29 Liang Y, Li Z, Huang Y, et al. ACS Nano, 2021, 15(4), 7078.
30 Wu M, Chen J, Huang W, et al. Biomacromolecules, 2020, 21(6), 2409.

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