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碳化血红素纳米颗粒在肿瘤微环境中增强氧化应激以促进光动力抗癌治疗

Light amplified oxidative stress in tumor microenvironment by carbonized hemin nanoparticles for boosting photodynamic anticancer therapy.

作者信息

Lin Liyun, Pang Wen, Jiang Xinyan, Ding Shihui, Wei Xunbin, Gu Bobo

机构信息

Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.

Biomedical Engineering Department, Peking University, Beijing, 100081, China.

出版信息

Light Sci Appl. 2022 Mar 1;11(1):47. doi: 10.1038/s41377-021-00704-5.

DOI:10.1038/s41377-021-00704-5
PMID:35228527
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8885839/
Abstract

Photodynamic therapy (PDT), which utilizes light excite photosensitizers (PSs) to generate reactive oxygen species (ROS) and consequently ablate cancer cells or diseased tissue, has attracted a great deal of attention in the last decades due to its unique advantages. However, the advancement of PDT is restricted by the inherent characteristics of PS and tumor microenvironment (TME). It is urgent to explore high-performance PSs with TME regulation capability and subsequently improve the therapeutic outcomes. Herein, we reported a newly engineered PS of polymer encapsulated carbonized hemin nanoparticles (P-CHNPs) via a facile synthesis procedure for boosting photodynamic anticancer therapy. Solvothermal treatment of hemin enabled the synthesized P-CHNPs to enhance oxidative stress in TME, which could be further amplified under light irradiation. Excellent in vitro and in vivo PDT effects were achieved due to the improved ROS (hydroxyl radicals and singlet oxygen) generation efficiency, hypoxia relief, and glutathione depletion. Moreover, the superior in vitro and in vivo biocompatibility and boosted PDT effect make the P-CHNPs a potential therapeutic agent for future translational research.

摘要

光动力疗法(PDT)利用光激发光敏剂(PSs)产生活性氧(ROS),进而消融癌细胞或病变组织,由于其独特优势,在过去几十年中备受关注。然而,PDT的进展受到PS固有特性和肿瘤微环境(TME)的限制。迫切需要探索具有TME调节能力的高性能PSs,从而提高治疗效果。在此,我们报道了一种新设计的聚合物包裹碳化血红素纳米颗粒(P-CHNPs)的PS,通过简便的合成程序来增强光动力抗癌治疗。对血红素进行溶剂热处理,使合成的P-CHNPs能够增强TME中的氧化应激,在光照下可进一步放大。由于提高了ROS(羟基自由基和单线态氧)的产生效率、缓解缺氧和消耗谷胱甘肽,实现了优异的体外和体内PDT效果。此外,P-CHNPs优异的体外和体内生物相容性以及增强的PDT效果使其成为未来转化研究的潜在治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/9f3e5ee0f566/41377_2021_704_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/4ad99a0c51be/41377_2021_704_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/8d5de35b2b5a/41377_2021_704_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/0d7b9e113fb6/41377_2021_704_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/9d3b36c972cb/41377_2021_704_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/b554c3f70653/41377_2021_704_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/b8947698be93/41377_2021_704_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/9f3e5ee0f566/41377_2021_704_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/4ad99a0c51be/41377_2021_704_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/8d5de35b2b5a/41377_2021_704_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/0d7b9e113fb6/41377_2021_704_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/9d3b36c972cb/41377_2021_704_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/b554c3f70653/41377_2021_704_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/b8947698be93/41377_2021_704_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/8885839/9f3e5ee0f566/41377_2021_704_Fig6_HTML.jpg

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