Nanoengineered CAR-T Biohybrids for Solid Tumor Immunotherapy with Microenvironment Photothermal-Remodeling Strategy.
Ze ChenHong PanYingmei LuoTing YinBaozhen ZhangJianhong LiaoMengmeng WangXiaofan TangGuojun HuangGuanjun DengMingbin ZhengLintao CaiPublished in: Small (Weinheim an der Bergstrasse, Germany) (2021)
Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable clinical success in eradicating hematologic malignancies. However, hostile microenvironment in solid tumors severely prevents CAR-T cells migrating, infiltrating, and killing. Herein, a nanoengineered CAR-T strategy is reported for enhancing solid tumor therapy through bioorthogonal conjugation with a nano-photosensitizer (indocyanine green nanoparticles, INPs) as a microenvironment modulator. INPs engineered CAR-T biohybrids (CT-INPs) not only retain the original activities and functions of CAR-T cells, but it is further armed with fluorescent tracing and microenvironment remodeling abilities. Irradiated with laser, CT-INPs demonstrate that mild photothermal intervention destroys the extracellular matrix, expanded blood vessels, loosened compact tissue, and stimulated chemokine secretion without damping CAR-T cell activities. Those regulations induce an immune-favorable tumor microenvironment for recruitment and infiltration of CT-INPs. CT-INPs triggered photothermal effects collapse the physical and immunological barriers of solid tumor, and robustly boosted CAR-T immunotherapy. Therefore, CAR-T biohybrids provide reliable treatment strategy for solid tumor immunotherapy via microenvironment reconstruction.
Keyphrases
- stem cells
- photodynamic therapy
- image quality
- computed tomography
- dual energy
- extracellular matrix
- contrast enhanced
- drug delivery
- cancer therapy
- randomized controlled trial
- positron emission tomography
- magnetic resonance imaging
- mental health
- drug release
- magnetic resonance
- mass spectrometry
- quantum dots
- high resolution
- mesenchymal stem cells
- bone marrow
- combination therapy
- label free