Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 29, Issue 13, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201807294
Keywords
atovaquone; hypoxia; indocyanine green; nanomedicine; photodynamic therapy
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Funding
- National Science and Technology Major Project [2017YFA0205400, 2018YFF0215500]
- National Natural Science Foundation of China [21474047, 51773089, 21874077, 21175075]
- Natural Science Foundation of Jiangsu Province [20181204]
- Science and Technology R&D Fund of Shenzhen City [JCYJ20170818110736342]
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Hypoxia, as characterized by the low local oxygen, confers on cancer cells resistance to oxygen-consuming photodynamic therapy (PDT). The limited success reached by current approaches harnessing reoxygenation to enhance PDT outcome promotes the reconsideration of the design of the therapeutic approach. In this study, a multistage delivery system capable of reversing hypoxia is demonstrated. Unlike previous strategies that only expect to affect the peripheral tumor tissue, the size-shrinkable system allows those deeply located hypoxia regions to be treated. Specifically, therapeutics, including atovaquone and indocyanine green derivatives that are respectively responsible for oxidative phosphorylation blockage and PDT, are encapsulated in a gelatin nanoparticle, whose structure would rupture to promote deep penetration when facing matrix metallopeptidase 2 enzyme overexpression in tumor tissue. The antihypoxic performance of the platform has been evaluated using a variety of analyses including flow-cytometry assay, immunofluorescence, and micro-positron-emission tomography imaging. Tumor regression in animal models confirms the feasibility and effectiveness of conquering the PDT-resistance through abrogating the oxygen consumption. It is hopeful that such a strategy could shed light on the development of next-generation PDT-adjuvant treatment.
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