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

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

  • Nat Commun. 2023 Aug 22;14(1):5111. doi: 10.1038/s41467-023-40814-9.
Lin Li 1,  Mengxing Zhang 2,  Jing Li 1,  Tiantian Liu 2,  Qixue Bao 1,  Xi Li 1,  Jiaying Long 3,  Leyao Fu 1,  Zhirong Zhang 3,  Shiqi Huang 2,  Zhenmi Liu 4,  Ling Zhang 5 6
Affiliations

Affiliations

  • 1 Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China.
  • 2 Med-X center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu, 610065, China.
  • 3 Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610065, China.
  • 4 Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China. liuzhenmi1983@hotmail.com.
  • 5 Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China. zhangling83@scu.edu.cn.
  • 6 Med-X center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu, 610065, China. zhangling83@scu.edu.cn.
PMID: 37607938 DOI: 10.1038/s41467-023-40814-9
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.

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