Journal
SMALL
Volume 16, Issue 23, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202001059
Keywords
BODIPY-vadimezan conjugate; core-shell electron transfer; hypoxic-and-metastatic tumors; type I photodynamic therapy; vascular-disruption
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Funding
- National Natural Science Foundation of China [61525402, 61775095]
- Jiangsu Provincial key research and development plan [BE2017741]
- Jiangsu Province Policy Guidance Plan [BZ2019014]
- Six talent peak innovation team in Jiangsu Province [TD-SWYY-009]
- Jiangsu Provincial Graduated Training Innovation Project [KYCX19_0862]
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Hypoxia severely impedes photodynamic therapy (PDT) efficiency. Worse still, considerable tumor metastasis will occur after PDT. Herein, an organic superoxide radical (O-2(center dot-)) nano-photogenerator as a highly effcient type I photosensitizer with robust vascular-disrupting efficiency to combat these thorny issues is designed. Boron difluoride dipyrromethene (BODIPY)-vadimezan conjugate (BDPVDA) is synthesized and enwrapped in electron-rich polymer-brushes methoxy-poly(ethylene glycol)-b-poly(2-(diisopropylamino) ethyl methacrylate) (mPEG- PPDA) to afford nanosized hydrophilic type I photosensitizer (PBV NPs). Owing to outstanding core-shell intermolecular electron transfer between BDPVDA and mPEG-PPDA, remarkable O-2(center dot-) can be produced by PBV NPs under near-infrared irradiation even in severe hypoxic environment (2% O-2), thus to accomplish effective hypoxic-tumor elimination. Simultaneously, the efficient ester-bond hydrolysis of BDPVDA in the acidic tumor microenvironment allows vadimezan release from PBV NPs to disrupt vasculature, facilitating the shut-down of metastatic pathways. As a result, PBV NPs will not only be powerful in resolving the paradox between traditional type II PDT and hypoxia, but also successfully prevent tumor metastasis after type I PDT treatment (no secondary-tumors found in 70 days and 100% survival rate), enabling enhancement of existing hypoxic-and-metastatic tumor treatment.
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