1. Academic Validation
  2. Cholesterol Metabolism Modulation Nanoplatform Improves Photo-Immunotherapeutic Effect In Oral Squamous Cell Carcinoma

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

  • Adv Healthc Mater. 2023 May 20;e2300018. doi: 10.1002/adhm.202300018.
Xinyu Zhang 1 Zichen Cao 1 Chuanhui Song 2 Zheng Wei 3 Meng Zhou 1 Si Chen 1 Jianchuan Ran 3 Hongbo Zhang 3 Huihui Zou 3 Shengwei Han 3 Yu Cai 4 Wei Han 3
Affiliations

Affiliations

  • 1 Department of Oral Medicine, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 30 Zhongyang Road, Nanjing, 210008, China.
  • 2 Institute of Translational Medicine, The Affiliated Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China.
  • 3 Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 30 Zhongyang Road, Nanjing, 210008, China.
  • 4 Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, 310014, China.
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) was 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. This article is protected by copyright. All rights reserved.

Keywords

cholesterol metabolism modulation; immunogenic cell death; immunotherapy; nanomedicine; oral squamous cell carcinoma.

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