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Background <p>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.</p> Methods <p>We prepared a hypoxia-responsive dendritic drug-drug conjugates IR806-(Azo-CB)<sub>4</sub>, 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.</p> Results <p>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.</p> Conclusions <p>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).</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月26日

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

摘要

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)4, 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).