Cholesterol removal improves performance of a model biomimetic system to co-deliver a photothermal agent and a STING agonist for cancer immunotherapy

Lin Li, Mengxing Zhang, Jing Li, Tiantian Liu, Qixue Bao, Xi Li, Jiaying Long, Leyao Fu, Zhirong Zhang, Shiqi Huang, Zhenmi Liu () and Ling Zhang ()
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Lin Li: Sichuan University
Mengxing Zhang: Sichuan University
Jing Li: Sichuan University
Tiantian Liu: Sichuan University
Qixue Bao: Sichuan University
Xi Li: Sichuan University
Jiaying Long: Sichuan University
Leyao Fu: Sichuan University
Zhirong Zhang: Sichuan University
Shiqi Huang: Sichuan University
Zhenmi Liu: Sichuan University
Ling Zhang: Sichuan University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Biological membranes often play important functional roles in biomimetic drug delivery systems. We discover that the circulation time and targeting capability of biological membrane coated nanovehicles can be significantly improved by reducing cholesterol level in the coating membrane. A proof-of-concept system using cholesterol-reduced and PD-1-overexpressed T cell membrane to deliver a photothermal agent and a STING agonist is thus fabricated. Comparing with normal membrane, this engineered membrane increases tumor accumulation by ~2-fold. In a melanoma model in male mice, tumors are eliminated with no recurrence in >80% mice after intravenous injection and laser irradiation; while in a colon cancer model in male mice, ~40% mice are cured without laser irradiation. Data suggest that the engineered membranes escape immune surveillance to avoid blood clearance while keeping functional surface molecules exposed. In summary, we develop a simple, effective, safe and widely-applicable biological membrane modification strategy. This “subtractive” strategy displays some advantages and is worth further development.

Date: 2023
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DOI: 10.1038/s41467-023-40814-9

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