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Hypoxia-responsive core-cross-linked supramolecular nanoprodrug based on dendritic drug-drug conjugates for
Yue Ding1, Yu Xie2, Liangshun Zheng2
1School of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019, P. R. China. yueding@ntu.edu.cn.
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).
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