Oxygen-self-supplying and HIF-1α inhibiting core-shell nano-system for hypoxia-resistant photodynamic therapy.
ACS applied materials & interfaces(2019)
摘要
Extreme hypoxia together with the expression of hypoxia inducible factor-1α (HIF-1α) represent significant barriers against the effective photodynamic therapy (PDT) of tumor. To mitigate these issues, we created a core-shell nano-system that can simultaneously alleviate tumor hypoxia and suppress the expression of HIF-1α to combat tumor resistance against PDT. Specifically, the carrier-free, dual-drug nano-core was formed by the self-assembly of hydrophobic photosensitizer (chlorin e6, Ce6) and rapamycin (RAP), and then the surface was coated by a layer of metal-organic frameworks (MOFs) to load catalase, reaching an overall drug loading of ~60%. In such system, catalase acted as oxygen-self-supplier to catalyze the decomposition of tumor abundant H2O2 into O2, and the sustained release of RAP down-regulated HIF-1α, which collectively potentiated the PDT efficacy against tumor. The nano-system could passively accumulate into tumor, realize in-situ oxygen generation and HIF-1α inhibition in tumor tissue, and thus exhibit strong PDT effect toward highly hypoxia tumor. This work provides a highly promising nano-platform to reverse hypoxia-mediated tumor resistance and overcome the restriction of PDT treatment.
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关键词
tumor therapy,self-oxygenation,nanomedicine,metal-organic framework,hypoxia
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