Inhibition of melanoma using a nanoceria-based prolonged oxygen-generating phototherapy hydrogel

Lidong Zhang; Xiaoguang Liu; Yinghua Mao; Shu Rong; Yonghong Chen; Yong Qi; Zhipeng Cai; Hong Li

doi:10.3389/fonc.2023.1126094

Inhibition of melanoma using a nanoceria-based prolonged oxygen-generating phototherapy hydrogel

Front Oncol. 2023 Mar 16:13:1126094. doi: 10.3389/fonc.2023.1126094. eCollection 2023.

Authors

Lidong Zhang¹, Xiaoguang Liu², Yinghua Mao³, Shu Rong³, Yonghong Chen³, Yong Qi⁴, Zhipeng Cai³, Hong Li³

Affiliations

¹ Institute of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China.
² Department of Gynecology, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, China.
³ Centre for Diseases Prevention and Control of Eastern Theater, Nanjing, China.
⁴ Huadong Research Institute for Medicine and Biotechniques, Nanjing, China.

Abstract

Tumor hypoxic environment is an inevitable obstacle for photodynamic therapy (PDT) of melanoma. Herein, a multifunctional oxygen-generating hydrogel loaded with hyaluronic acid-chlorin e6 modified nanoceria and calcium peroxide (Gel-HCeC-CaO₂) was developed for the phototherapy of melanoma. The thermo-sensitive hydrogel could act as a sustained drug delivery system to accumulate photosensitizers (chlorin e6, Ce6) around the tumor, followed by cellular uptake mediated by nanocarrier and hyaluronic acid (HA) targeting. The moderate sustained oxygen generation in the hydrogel was produced by the reaction of calcium peroxide (CaO₂) with infiltrated H₂O in the presence of catalase mimetic nanoceria. The developed Gel-HCeC-CaO₂ could efficiently alleviate the hypoxia microenvironment of tumors as indicated by the expression of hypoxia-inducible factor -1α (HIF-1α), meeting the "once injection, repeat irradiation" strategy and enhanced PDT efficacy. The prolonged oxygen-generating phototherapy hydrogel system provided a new strategy for tumor hypoxia alleviation and PDT.

Keywords: hydrogel; hypoxia alleviation; melanoma; nanaoceria; photodynamic therapy.

Grants and funding

This work was supported by research grants from the National Natural Science Foundation of China (81803173 and 81901555), Natural Science Foundation of Jiangsu Province (SBK2018040981), Incubation Project of Military Medical Science and Technology (20QNPY121), and Youth Science and Technology Project (grant no. (2022)-151).