Near-Infrared Light-Responsive Liposomes for Modulating Switchable CAR-T Cell Therapy
- 1School of Pharmacy, Naval Medical University, Shanghai, People’s Republic of China
- 2School of Pharmaceutical Sciences, Anhui Medical University, Hefei, People’s Republic of China
- 3General Office, Shanghai Municipal Health Commission, Shanghai, People’s Republic of China
Abstract
Introduction: Chimeric antigen receptor T (CAR-T) cell therapy has great potential but is limited by off-target effects and cytokine release syndrome. To address these challenges, we developed a mesothelin-targeted switchable CAR-T cell system whose activity can be externally controlled by near-infrared (NIR) light-responsive liposomes.
Methods: We constructed mesothelin-targeted switchable CAR-T cells via lentiviral transduction. A NIR-responsive liposomal formulation was prepared to encapsulate a small-molecule switch agent (rapamycin or AP21967) for controlled release upon NIR irradiation. By encapsulating a NIR-triggerable photosensitizer, the liposomes became photo-labile, and exposure to 730 nm light induced lipid peroxidation, consequently allowing drug release. The switchable CAR-T cells were co-cultured with mesothelin-expressing ovarian cancer cells (OVCAR-3) under various conditions, with or without NIR irradiation. Cytotoxicity was assessed by LDH release assay, and cytokine secretion (TNF-α and IL-2) was measured by ELISA.
Results: The switchable CAR-T cells exhibited minimal baseline cytotoxicity in the absence of the inducing agent. Upon NIR irradiation, the liposomes released the encapsulated switch agent, which activated the CAR-T cells in a concentration-dependent manner. NIR-triggered activation significantly enhanced the secretion of TNF-α and IL-2 and potentiated the killing effect against mesothelin-positive ovarian cancer cells in vitro.
Conclusion: Our findings demonstrate that the combination of switchable CAR-T technology with NIR-responsive liposomes enables spatiotemporally controlled CAR-T activation, offering a potential strategy to mitigate off-target toxicity and facilitating the clinical application of CAR-T therapy in solid tumors.
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BibTeX
@article{lu2026nearinfrared,
title = {{Near-Infrared Light-Responsive Liposomes for Modulating Switchable CAR-T Cell Therapy}},
author = {Guangzhao Lu and He Zhang and Huan Wang and Xiqing Gao and Kuizhi Zhang and Yangyuyuan Song and Lijia Kong and Min Zhu and Hao Zou and Ying Lu},
journal = {International Journal of Nanomedicine},
year = {2026},
month = oct,
doi = {10.2147/ijn.s630008},
url = {https://doi.org/10.2147/ijn.s630008},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Near-Infrared Light-Responsive Liposomes for Modulating Switchable CAR-T Cell Therapy
AU - Guangzhao Lu
AU - He Zhang
AU - Huan Wang
AU - Xiqing Gao
AU - Kuizhi Zhang
AU - Yangyuyuan Song
AU - Lijia Kong
AU - Min Zhu
AU - Hao Zou
AU - Ying Lu
PY - 2026
DA - 2026/10/26
JO - International Journal of Nanomedicine
DO - 10.2147/ijn.s630008
UR - https://doi.org/10.2147/ijn.s630008
AB - Introduction: Chimeric antigen receptor T (CAR-T) cell therapy has great potential but is limited by off-target effects and cytokine release syndrome. To address these challenges, we developed a mesothelin-targeted switchable CAR-T cell system whose activity can be externally controlled by near-infrared (NIR) light-responsive liposomes. Methods: We constructed mesothelin-targeted switchable CAR-T cells via lentiviral transduction. A NIR-responsive liposomal formulation was prepared to encapsulate a small-molecule switch agent (rapamycin or AP21967) for controlled release upon NIR irradiation. By encapsulating a NIR-triggerable photosensitizer, the liposomes became photo-labile, and exposure to 730 nm light induced lipid peroxidation, consequently allowing drug release. The switchable CAR-T cells were co-cultured with mesothelin-expressing ovarian cancer cells (OVCAR-3) under various conditions, with or without NIR irradiation. Cytotoxicity was assessed by LDH release assay, and cytokine secretion (TNF-α and IL-2) was measured by ELISA. Results: The switchable CAR-T cells exhibited minimal baseline cytotoxicity in the absence of the inducing agent. Upon NIR irradiation, the liposomes released the encapsulated switch agent, which activated the CAR-T cells in a concentration-dependent manner. NIR-triggered activation significantly enhanced the secretion of TNF-α and IL-2 and potentiated the killing effect against mesothelin-positive ovarian cancer cells in vitro. Conclusion: Our findings demonstrate that the combination of switchable CAR-T technology with NIR-responsive liposomes enables spatiotemporally controlled CAR-T activation, offering a potential strategy to mitigate off-target toxicity and facilitating the clinical application of CAR-T therapy in solid tumors.
SN - 1176-9114
SN - 1178-2013
ER -