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基于树枝状药物-药物共轭物的缺氧响应性核心交联超分子纳米前药用于协同抗癌治疗

Hypoxia-responsive core-cross-linked supramolecular nanoprodrug based on dendritic drug-drug conjugates for synergetic anticancer therapy.

作者信息

Ding Yue, Xie Yu, Zheng Liangshun, Lin Mingguang, Shi Yihai, Chen Tingting, Du Chang, Ding Jin, Ning Beifang

机构信息

School of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019, P. R. China.

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China.

出版信息

J Nanobiotechnology. 2025 Apr 26;23(1):316. doi: 10.1186/s12951-025-03394-y.

DOI:10.1186/s12951-025-03394-y
PMID:40287727
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12032639/
Abstract

BACKGROUND

Recently, the strategy of self-assembling dendritic drug-drug conjugates into supramolecular nanoprodrug was widely explored in biomedical applications. Herein, we construct a hypoxia-responsive core-cross-linked supramolecular nanoprodrug (CSN-IR806/CB) based on a dendritic drug-drug conjugate.

METHODS

We prepared a hypoxia-responsive dendritic drug-drug conjugates IR806-(Azo-CB), which was combined with β-cyclodextrin-pendant poly(ethylene glycol)-block-poly(glutamic acid) block copolymer (PEG-PGlu-CD) to construct the core-cross-linked supramolecular nanoprodrug (CSN-IR806/CB) with enhanced physiological stability through the synergy of π-π stacking interaction, host-guest complexation, hydrogen bonds, and hydrophobic interaction.

RESULTS

The near-infrared (NIR) light irradiation of the CSN-IR806/CB treated tumor cells induced IR806-mediated PDT and PTT, and aggravated hypoxia, which triggered the disassembly of CSN-IR806/CB and the subsequent release of activated CB for synergetic cancer cell killing.

CONCLUSIONS

The CSN-IR806/CB can realize a synergistic triple therapeutic effect of photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy (CT; i.e., PTT-PDT-CT).

摘要

背景

近年来，将树枝状药物 - 药物共轭物自组装成超分子纳米前药的策略在生物医学应用中得到了广泛探索。在此，我们基于树枝状药物 - 药物共轭物构建了一种缺氧响应性核心交联超分子纳米前药（CSN - IR806/CB）。

方法

我们制备了一种缺氧响应性树枝状药物 - 药物共轭物IR806 - (Azo - CB)，将其与β - 环糊精 - 侧链聚（乙二醇） - 嵌段 - 聚（谷氨酸）嵌段共聚物（PEG - PGlu - CD）结合，通过π - π堆积相互作用、主客体络合、氢键和疏水相互作用的协同作用构建具有增强生理稳定性的核心交联超分子纳米前药（CSN - IR806/CB）。

结果

用CSN - IR806/CB处理的肿瘤细胞经近红外（NIR）光照射诱导了IR806介导的光动力疗法（PDT）和光热疗法（PTT），并加重了缺氧，这触发了CSN - IR806/CB的解体以及随后活化的CB的释放，用于协同杀伤癌细胞。

结论

CSN - IR806/CB可以实现光热疗法（PTT）、光动力疗法（PDT）和化疗（CT，即PTT - PDT - CT）的协同三重治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/694b25318127/12951_2025_3394_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/79b074995819/12951_2025_3394_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/b1654a5eb973/12951_2025_3394_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/8993e8806f8a/12951_2025_3394_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/14899da0170a/12951_2025_3394_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/652155eed251/12951_2025_3394_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/3c5941c9aa62/12951_2025_3394_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/3f332dd10d11/12951_2025_3394_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/694b25318127/12951_2025_3394_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/79b074995819/12951_2025_3394_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/b1654a5eb973/12951_2025_3394_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/8993e8806f8a/12951_2025_3394_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/14899da0170a/12951_2025_3394_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/652155eed251/12951_2025_3394_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/3c5941c9aa62/12951_2025_3394_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/3f332dd10d11/12951_2025_3394_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267e/12032639/694b25318127/12951_2025_3394_Fig7_HTML.jpg

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