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用于缺氧肿瘤光动力治疗的过氧化氢响应性和氧气保留纳米乳液的正交优化、表征及体外抗癌活性评价

Orthogonal Optimization, Characterization, and In Vitro Anticancer Activity Evaluation of a Hydrogen Peroxide-Responsive and Oxygen-Reserving Nanoemulsion for Hypoxic Tumor Photodynamic Therapy.

作者信息

Hong Liang, Wang Jianman, Zhou Yi, Shang Guofu, Guo Tao, Tang Hailong, Li Jiangmin, Luo Yali, Zeng Xiangyu, Zeng Zhu, Hu Zuquan

机构信息

Key Laboratory of Infectious Immune and Antibody Engineering in University of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, School of Basic Medical Sciences/School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang 550025, China.

Immune Cells and Antibody Engineering Research Center in University of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China.

出版信息

Cancers (Basel). 2023 Mar 3;15(5):1576. doi: 10.3390/cancers15051576.

DOI:10.3390/cancers15051576
PMID:36900370
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10000418/
Abstract

Tumor hypoxia can seriously impede the effectiveness of photodynamic therapy (PDT). To address this issue, two approaches, termed in situ oxygen generation and oxygen delivery, were developed. The in situ oxygen generation method uses catalysts such as catalase to decompose excess HO produced by tumors. It offers specificity for tumors, but its effectiveness is limited by the low HO concentration often present in tumors. The oxygen delivery strategy relies on the high oxygen solubility of perfluorocarbon, etc., to transport oxygen. It is effective, but lacks tumor specificity. In an effort to integrate the merits of the two approaches, we designed a multifunctional nanoemulsion system named CCIPN and prepared it using a sonication-phase inversion composition-sonication method with orthogonal optimization. CCIPN included catalase, the methyl ester of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me), photosensitizer IR780, and perfluoropolyether. Perfluoropolyether may reserve the oxygen generated by catalase within the same nanoformulation for PDT. CCIPN contained spherical droplets below 100 nm and showed reasonable cytocompatibility. It presented a stronger ability to generate cytotoxic reactive oxygen species and consequently destroy tumor cells upon light irradiation, in comparison with its counterpart without catalase or perfluoropolyether. This study contributes to the design and preparation of oxygen-supplementing PDT nanomaterials.

摘要

肿瘤缺氧会严重阻碍光动力疗法（PDT）的疗效。为了解决这个问题，人们开发了两种方法，即原位产氧和氧输送。原位产氧方法使用过氧化氢酶等催化剂来分解肿瘤产生的过量过氧化氢。它对肿瘤具有特异性，但其有效性受到肿瘤中通常存在的低过氧化氢浓度的限制。氧输送策略依靠全氟碳等的高氧溶解度来输送氧气。它是有效的，但缺乏肿瘤特异性。为了整合这两种方法的优点，我们设计了一种名为CCIPN的多功能纳米乳液系统，并采用正交优化的超声相转变组成-超声法制备了该系统。CCIPN包含过氧化氢酶、2-氰基-3,12-二氧代齐墩果-1,9(11)-二烯-28-酸甲酯（CDDO-Me）、光敏剂IR780和全氟聚醚。全氟聚醚可以将过氧化氢酶产生的氧气保留在同一纳米制剂中用于光动力疗法。CCIPN含有直径小于100nm的球形液滴，并表现出合理的细胞相容性。与不含过氧化氢酶或全氟聚醚的对照物相比，它在光照下表现出更强的产生细胞毒性活性氧的能力，从而破坏肿瘤细胞。这项研究有助于补充氧气的光动力疗法纳米材料的设计和制备。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/cde287a4416b/cancers-15-01576-g016.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/489ea96ac787/cancers-15-01576-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/c67165795469/cancers-15-01576-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/e9c7c401d648/cancers-15-01576-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/71e6e41dd816/cancers-15-01576-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/5690756a292e/cancers-15-01576-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/8721042735b5/cancers-15-01576-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/cde287a4416b/cancers-15-01576-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/c8bb8e504282/cancers-15-01576-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/c2e8e26406d0/cancers-15-01576-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/53c1d442f003/cancers-15-01576-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/222fb616c92f/cancers-15-01576-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/c05bccdcaf3f/cancers-15-01576-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/3d5d7ad6f9ba/cancers-15-01576-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/489ea96ac787/cancers-15-01576-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/c67165795469/cancers-15-01576-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/e9c7c401d648/cancers-15-01576-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/71e6e41dd816/cancers-15-01576-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/5690756a292e/cancers-15-01576-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/8721042735b5/cancers-15-01576-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce92/10000418/cde287a4416b/cancers-15-01576-g016.jpg

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