Multifunctional liposomes remodeling tumor microenvironment for enhancing Hemoporfin-mediated photodynamic therapy

Abstract

Photodynamic therapy (PDT) utilizes light and photosensitizer (PS) to generate reactive oxygen species (ROS) to kill cancer cells, presenting a promising strategy as an anti-cancer treatment. However, the low hydrophilicity and poor targeting of currently used PSs, as well as the abnormal tumor microenvironment (TME), limit the clinical application of PDT. Herein, non-toxic liposomes with the ability to incorporate both hydrophilic and hydrophobic PS are used as the nanocarrier to co-load Hemoporfin, L-buthionine sulfoximine (BSO), and catalase (CAT) to obtain BSO/CAT@Liposomes-Hemoporfin nanoparticles (BCHL NPs), which could be used to remodel the TME and to enhance Hemoporfin-mediated PDT efficacy. BCHL NPs exhibit a long blood circulation time and can accumulate in the tumor. BSO can reduce the cytosolic concentration of glutathione (GSH), a natural scavenger of ROS. CAT catalyzes the endogenously overexpressed H₂O₂ in the tumor site into H₂O and O₂, thus relieving tumor hypoxia and enhancing ROS generation. Upon irradiation, the synergetic effects of reduced GSH synthesis by BSO and relieved hypoxia by CAT were observed in 4T1 tumor-bearing mouse model. Compared to the tumor treated by free Hemoporfin, BCHL NPs-mediated PDT resulted in 1.25-fold higher inhibition of tumor growth due to the enhanced ROS generation. The present study provides insight into the design of efficient strategies for enhanced clinic Hemoporfin-mediated PDT efficiency.

Keywords

BSO/CAT@Liposomes-Hemoporfin nanoparticles (BCHL NPs) / enhancement / Hemoporfin / liposomes / photodynamic therapy (PDT) / singlet oxygen generation / tumor microenvironment (TME)

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2025 The Author(s). BMEMat published by John Wiley & Sons Australia, Ltd on behalf of Shandong University.