光动力疗法
光敏剂
癌症研究
沸石咪唑盐骨架
肿瘤缺氧
生物物理学
化学
材料科学
单线态氧
医学
药理学
氧气
金属有机骨架
放射治疗
内科学
生物
吸附
有机化学
作者
Danyang Chen,Meng Suo,Guo Liang Jiang,Wenxue Tang,Wei Jiang,Ying Li,Yanhong Duo
标识
DOI:10.1002/adhm.202001577
摘要
Significant progress has been made in the use of phycocyanin (PC) as a photosensitizer (PS) agent for photodynamic therapy (PDT). The clinical use of PC, however, has been limited by its poor stability, unfavorable pharmacokinetics, limited tumor cell uptake, and the hypoxic nature of the tumor microenvironment. In this study, a novel biomimetic mineralization approach is described for encapsulating PC using zeolitic imidazolate framework-8 (ZIF-8), after which MPEG2000 -COOH is further utilized as an anchor on the ZIF/PC complex in order to yield MPEG2000 -ZIF/PC composites (PMs). These PMs are then used as a stable reinforced PS for PDT, effectively improving the intracellular delivery of this protein PS. In contrast to prior studies that have sought to overcome intratumoral hypoxia via increasing oxygen delivery to the tumor site, the mitochondrial complex I inhibitor papaverine (PPV) is instead utilized to reduce intratumor oxygen consumption in an effort to augment the PDT efficacy of the PMs. It is found that this combination treatment strategy markedly improves the antitumor properties of these PMs both in vitro and in patient-derived xenograft (PDX) models without inducing significant side effects. It is therefore proposed that the "armor-plating" of protein PS agents with ZIF-8 in combination with PPV may be a promising approach to precision medicine-mediated tumor treatment.
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