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

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.

Research Progress in Oxygen Carrier Design and Application

“…In addition, perfluorocarbons can dissolve oxygen and retain the oxygen produced by catalase decomposing H 2 O 2 inside the tumor in perfluorocarbons to achieve synergistic PDT. 105 The nano-PFC oxygen carrier can also design a pH-responsive PFC oxygen carrier according to the acidic environment inside the tumor, and the tumor inhibition rate reaches 84.2%. 106 PFC oxygen carriers can also enhance the photothermal therapy (PPT) of tumors.…”

“…Wu et al created oxygen self-enhanced photodynamic therapy by loading photosensitizers into PFC nanodroplets, with a tumor inhibition rate approaching 80% (Figure B). In addition, perfluorocarbons can dissolve oxygen and retain the oxygen produced by catalase decomposing H 2 O 2 inside the tumor in perfluorocarbons to achieve synergistic PDT . The nano-PFC oxygen carrier can also design a pH-responsive PFC oxygen carrier according to the acidic environment inside the tumor, and the tumor inhibition rate reaches 84.2% .…”