光动力疗法
材料科学
缺氧(环境)
流式细胞术
生物物理学
肿瘤缺氧
癌症研究
化学
生物医学工程
活性氧
纳米技术
细胞生物学
医学
氧气
生物
免疫学
外科
有机化学
放射治疗
作者
Donglin Xia,Peipei Xu,Xingyu Luo,Jianfeng Zhu,Haiying Gu,Da Huo,Yong Hu
标识
DOI:10.1002/adfm.201807294
摘要
Abstract 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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