In Situ Injectable Sequentially Responsive Hydrogel Based on Triblock Copolymers for Breast Cancer Theranostic Amplification

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2025-06-09 DOI:10.1021/acs.biomac.5c00320

Yuxi Chen , Qiongxue Huang , Xueqiang Nie , Qingqin He , Jiawen Zhang , Tonghe Liu , Sichao Tian , Yihang Li , Zhaocui Sun , Zhonghao Sun , Guoxu Ma , Haitao Liu

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Abstract

Celastrol (Cel), a natural small molecule, effectively inhibits breast cancer but has poor solubility and systemic toxicity. Herein, an in situ injectable sequentially responsive celastrol hydrogel (FCPC) based on the temperature-sensitive poloxamer F127 and tumor-acidity-cleavable maleic acid amide is rationally designed. Once injected into tumor tissue, FCPC forms a stable gel state rapidly, followed by continuously releasing activity molecules for five days. This injectable thermosensitive drug delivery system extends the drug residence time and targeted release. The platform greatly strengthens the Cel’s antitumor ability both in vitro and in vivo and meanwhile reduces cancer metastasis and toxic side effects. Studies suggest FCPC may act by suppressing PI3K-Akt and MAPK pathways. Such an injectable sequentially responsive hydrogel intelligently solves the administration problem caused by poor solubility of natural small molecule and has the potential for clinical applicability.

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基于三嵌段共聚物的原位可注射顺序反应水凝胶用于乳腺癌治疗扩增。

Celastrol （Cel）是一种天然小分子，可有效抑制乳腺癌，但其溶解度差且具有全身毒性。基于温度敏感的波洛沙姆F127和肿瘤酸可切割的马来酸酰胺，合理设计了一种原位可注射顺序反应的雷公酚水凝胶（FCPC）。FCPC一旦注射到肿瘤组织中，迅速形成稳定的凝胶状态，随后连续5天释放活性分子。该注射热敏给药系统延长了药物停留时间和靶向释放。该平台大大增强了细胞体外和体内的抗肿瘤能力，同时减少了癌细胞的转移和毒副作用。研究表明FCPC可能通过抑制PI3K-Akt和MAPK通路起作用。该可注射顺序反应水凝胶智能地解决了天然小分子溶解度差引起的给药问题，具有临床应用潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.