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温度-离子- pH三重响应型结冷胶原位水凝胶用于长效癌症治疗

Temperature-Ion-pH Triple Responsive Gellan Gum as In Situ Hydrogel for Long-Acting Cancer Treatment.

作者信息

Zhou Shuwen, Zheng Xinmeng, Yi Ke, Du Xuancheng, Wang Cheng, Cui Pengfei, Jiang Pengju, Ni Xinye, Qiu Lin, Wang Jianhao

机构信息

School of Pharmacy, Changzhou University, Changzhou 213164, China.

The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, China.

出版信息

Gels. 2022 Aug 15;8(8):508. doi: 10.3390/gels8080508.

DOI:10.3390/gels8080508
PMID:36005109
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9407511/
Abstract

BACKGROUND

Promising cancer chemotherapy requires the development of suitable drug delivery systems (DDSs). Previous research has indicated that a hydrogel is a powerful DDS for tumor therapy and holds great potential to offer a feasible method for cancer management.

METHODS

In this study, glutathione-gellan gum conjugate (GSH-GG) was synthesized through chemical reaction. Doxorubicin hydrochloride (DOX) was loaded into GSH-GG to accomplish DOX-loaded GSH-GG. The properties, injectability, drug release, and in vitro and in vivo anticancer effects of DOX-loaded GSH-GG were tested.

RESULTS

DOX-loaded GSH-GG showed a temperature-ion dual responsive gelling property with good viscosity, strength, and injectability at an optimized gel concentration of 1.5%. In addition, lower drug release was found under acidic conditions, offering beneficial long-acting drug release in the tumor microenvironment. DOX-loaded GSH-GG presented selective action by exerting substantially higher cytotoxicity on cancer cells (4T1) than on normal epithelial cells (L929), signifying the potential of complete inhibition of tumor progression, without affecting the health quality of the subjects.

CONCLUSIONS

GSH-GG can be applied as a responsive gelling material for delivering DOX for promising cancer therapy.

摘要

背景

有前景的癌症化疗需要开发合适的药物递送系统(DDSs)。先前的研究表明,水凝胶是一种强大的肿瘤治疗DDS,具有为癌症管理提供可行方法的巨大潜力。

方法

在本研究中,通过化学反应合成了谷胱甘肽-结冷胶共轭物(GSH-GG)。将盐酸多柔比星(DOX)负载到GSH-GG中以制备负载DOX的GSH-GG。测试了负载DOX的GSH-GG的性质、可注射性、药物释放以及体外和体内抗癌效果。

结果

负载DOX的GSH-GG在1.5%的优化凝胶浓度下表现出温度-离子双重响应凝胶特性,具有良好的粘度、强度和可注射性。此外,在酸性条件下发现较低的药物释放,这有利于在肿瘤微环境中实现长效药物释放。负载DOX的GSH-GG对癌细胞(4T1)的细胞毒性明显高于正常上皮细胞(L929),表现出选择性作用,这意味着在不影响受试者健康质量的情况下完全抑制肿瘤进展的潜力。

结论

GSH-GG可作为一种响应性凝胶材料用于递送DOX,有望用于癌症治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/8036e88da507/gels-08-00508-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/47aeec64be72/gels-08-00508-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/af8b87a88bfe/gels-08-00508-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/f1e7465ac9b1/gels-08-00508-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/f9646e257bd0/gels-08-00508-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/cbe00373a7d2/gels-08-00508-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/8036e88da507/gels-08-00508-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/47aeec64be72/gels-08-00508-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/af8b87a88bfe/gels-08-00508-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/f1e7465ac9b1/gels-08-00508-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/f9646e257bd0/gels-08-00508-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/cbe00373a7d2/gels-08-00508-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358c/9407511/8036e88da507/gels-08-00508-g006.jpg

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