Cholesterol removal improves performance of a model biomimetic system to co-deliver a photothermal agent and a STING agonist for cancer immunotherapy
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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. On melanoma mice model, tumors are eliminated with no recurrence in >80% mice after intravenous injection and laser irradiation; while on colon cancer mice model, ~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 unique advantages and is worth further development.
INSTRUMENT(S): Q Exactive
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): T Cell, Blood Serum
DISEASE(S): Colon Cancer
SUBMITTER:
Lin Li
LAB HEAD: Lin Li
PROVIDER: PXD044151 | Pride | 2023-08-02
REPOSITORIES: Pride
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