Cholesterol Metabolism Modulation Nanoplatform Improves Photo-Immunotherapeutic Effect in Oral Squamous Cell Carcinoma.

Abstract

Impressive results in cancer treatment have been obtained through immunotherapy. However, abnormally high cholesterol metabolism in the tumor microenvironment (TME) leads to poor immunogenicity or even immunosuppression, which dramatically reduces the clinical response of patients with oral squamous cell carcinoma (OSCC) to immunotherapy. In this study, a cholesterol-modulating nanoplatform (PYT NP) is developed to restore the normal immune microenvironment, significantly inhibiting SQLE (an essential gene for cholesterol biosynthesis in tumor cells) by releasing terbinafine, thereby reducing cholesterol in the TME and suppressing tumor cell proliferation. In addition, the nanoplatform is equipped with a second near-infrared (NIR-II) photosensitizer, Y8, which triggers immunogenic cell death of tumor cells, thereby promoting intra-tumor infiltration and immune activation via the production of damage-associated molecular patterns for photoimmunotherapy. PYT NPs show great promise in stimulating strong cholesterol-modulating anticancer immunity combined with photoimmunotherapy, opening up a new avenue for sensitized OSCC immunotherapy.

• Authors: Xinyu Zhang, Zichen Cao, Chuanhui Song, Zheng Wei, Meng Zhou, Si Chen, Jianchuan Ran, Hongbo Zhang, Huihui Zou, Shengwei Han, Yu Cai, Wei Han
• Journal: Advanced healthcare materials (Adv Healthc Mater) Vol. 12 Issue 22 Pg. e2300018 (09 2023) ISSN: 2192-2659 [Electronic] Germany
• PMID: 37209373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Wiley-VCH GmbH.

Topics

• Humans
• Carcinoma, Squamous Cell (drug therapy)
• Mouth Neoplasms (drug therapy)
• Squamous Cell Carcinoma of Head and Neck
• Neoplasms (therapy)
• Immunotherapy (methods)
• Head and Neck Neoplasms
• Tumor Microenvironment
• Cell Line, Tumor