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富氧纳米乳的合理设计用于增强近红外激光激活光动力学疗法治疗缺氧肿瘤。

Rational design of an oxygen-enriching nanoemulsion for enhanced near-infrared laser activatable photodynamic therapy against hypoxic tumors.

机构信息

Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China.

School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China.

出版信息

Colloids Surf B Biointerfaces. 2021 Feb;198:111500. doi: 10.1016/j.colsurfb.2020.111500. Epub 2020 Dec 1.

DOI:10.1016/j.colsurfb.2020.111500
PMID:33303318
Abstract

Photodynamic therapy (PDT) has emerged as one of the most promising modalities to treat cancers. However, the hypoxic microenvironment in tumors severely limits the efficiency of PDT. IR780 is a near-infrared light activatable photosensitizer for PDT. It has attracted intensive attention owing to its intriguing properties such as mitochondria-targeting ability and fluorescence imaging capability. Nevertheless, its application in tumor treatment is hampered by its low aqueous solubility and poor stability. To address these obstacles, here we designed a novel hierarchical nanoplatform containing a uniquely stable high loading capacity oxygen carrier (perfluoropolyether, in short, PFPE) and IR780. This nanoplatform (IR780-P/W NE, in abbreviation for IR780-PFPE-in-water nanoemulsion) has no detectable dark cytotoxicity. It not only improves the aqueous solubility and stability of IR780, but also transports oxygen to relieve hypoxia and boosts the efficiency of near-infrared light triggered PDT via augmentation of reactive oxygen species generation. Particularly, the innovative nanosized oxygen carrier developed in this research, P/W NE, is a potential universal platform for loading hydrophobic photosensitizers (including but not limited to IR780), sonosensitizers, or radiosensitizers, and simultaneously improving the therapeutic efficacy. Our results highlight the intriguing potential of the developed nanoemulsions for mitigating tumor hypoxia and enhancing the efficiencies of oxygen-dependent therapies including PDT, sonodynamic therapy, radiotherapy, and so on.

摘要

光动力疗法 (PDT) 已成为治疗癌症最有前途的方法之一。然而,肿瘤中的缺氧微环境严重限制了 PDT 的效率。IR780 是一种近红外光激活的光敏剂,用于 PDT。由于其独特的性质,如靶向线粒体的能力和荧光成像能力,引起了人们的广泛关注。然而,其在肿瘤治疗中的应用受到其低水溶性和差稳定性的限制。为了解决这些障碍,我们设计了一种新型的包含独特稳定的高载氧体(全氟聚醚,简称 PFPE)和 IR780 的分层纳米平台。这种纳米平台(IR780-P/W NE,简称 IR780-PFPE-水纳米乳)没有可检测的暗毒性。它不仅提高了 IR780 的水溶性和稳定性,而且通过增加活性氧的产生来输送氧气以缓解缺氧,并通过增强近红外光触发 PDT 的效率。特别是,本研究中开发的创新纳米级氧载体 P/W NE 是一种潜在的通用平台,可用于装载疏水性光敏剂(包括但不限于 IR780)、声敏剂或放射敏剂,同时提高治疗效果。我们的结果突出了开发的纳米乳在减轻肿瘤缺氧和增强包括 PDT、声动力疗法、放射疗法等氧依赖性治疗的效率方面的潜在潜力。

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