Preparation method and application of CAR-T (Chimeric Antigen Receptor-T) cell loaded with biological calcified nanomaterial

By preparing BCLT, a biocalcified nanomaterial with mitochondrial targeting on its surface, and linking it to CAR-T cells, the problems of poor infiltration effect and immunosuppressive microenvironment of CAR-T cells in solid tumor treatment were solved, achieving highly efficient tumor killing and infiltration effects, and improving treatment efficacy and mouse survival rate.

CN122097569APending Publication Date: 2026-05-29XUZHOU MEDICAL UNIVERSITY
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Patent Information

Application Number
CN202610257658.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-03-04
Publication Date
2026-05-29

AI Technical Summary

Technical Problem

CAR-T cell therapy for solid tumors suffers from poor infiltration, an acidic immunosuppressive microenvironment in the tumor, insufficient target specificity, and issues related to carrier toxicity and biocompatibility. Existing biomaterial carrier delivery systems cannot effectively improve the immunosuppressive microenvironment and have insufficient targeting efficiency.

Method used

Using a biocalcified nanomaterial (BCLT) preparation method, black phosphorus quantum dots, calcium peroxide and lipid components are mixed, ultrasonically emulsified and purified by ultrafiltration centrifugation to prepare BCLT with mitochondrial targeting molecules on the surface. These BCLTs are then linked to the surface of CAR-T cells via disulfide bonds, enabling the release of black phosphorus quantum dots after tumor cell endocytosis to promote oxidative phosphorylation, improve the immunosuppressive microenvironment, and achieve precise delivery by combining mitochondrial targeting and chemical bond stability.

Benefits of technology

In in vitro experiments, CAR-T cells loaded with biocalcified nanomaterials significantly improved the killing effect and tumor spheroid infiltration capacity. In in vivo experiments, the tumor infiltration capacity and therapeutic effect were the best, improving the survival rate of mice and alleviating the problem of tumor heterogeneity of CAR-T cells.

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Abstract

The invention is suitable for the technical field of biological medicine, and provides a preparation method and application of a CAR-T cell loaded with a biological calcified nanometer.The method comprises the steps that 1, black phosphorus quantum dots, calcium peroxide and lipid components are mixed, and BCLT with the surface modified with mitochondrial targeting molecule triphenylphosphine is obtained through ultrasonic emulsification and ultrafiltration centrifugal purification; step 2, dyeing the CAR-T cells and a membrane dye, and then adding a reduction response type connecting arm DSPE-S-S-NHS containing a disulfide bond to carry out co-incubation; and step 3, co-incubating BCLT and the CAR-T cells, so that the BCLT is connected to the surfaces of the CAR-T cells through chemical bonds, and the CAR-T cells loaded with the biological calcified nanometers.The infiltration capacity and killing effect of the CAR-T cells on solid tumors are remarkably improved, the problem of tumor heterogeneity can be relieved, and the CAR-T cells loaded with the biological calcified nanometers.The CAR-T cells loaded with the biological calcified nanometersare excellent in biological safety and synergistic anti-tumor effect.
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