Orthogonal Optimization, Characterization, and In Vitro Anticancer Activity Evaluation of a Hydrogen Peroxide-Responsive and Oxygen-Reserving Nanoemulsion for Hypoxic Tumor Photodynamic Therapy
Author:
Hong Liang12ORCID, Wang Jianman1, Zhou Yi12, Shang Guofu1, Guo Tao12, Tang Hailong1, Li Jiangmin12, Luo Yali12, Zeng Xiangyu12, Zeng Zhu1ORCID, Hu Zuquan123ORCID
Affiliation:
1. 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 2. 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 3. Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education of China, Guizhou Medical University, Guiyang 550025, China
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 H2O2 produced by tumors. It offers specificity for tumors, but its effectiveness is limited by the low H2O2 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.
Funder
National Natural Science Foundation of China Guizhou Provincial Science and Technology Projects Youth Science and Technology Talents Growth Project of Guizhou Ordinary Colleges and Universities Science and Technology Fund Project of Guizhou Provincial Health Commission Excellent Young Talents Plan of Guizhou Medical University Cultivation Project for National Natural Science Foundation of China High-Level Talent Initiation Project of Guizhou Medical University
Subject
Cancer Research,Oncology
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