期刊
THERANOSTICS
卷 11, 期 14, 页码 6860-6872出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.57511
关键词
magnetic hyperthermia; CSF1R inhibitor; tumor microenvironment; tumor-associated macrophage; immune memory; targeted delivery; magnetic liposomes
资金
- National Key Research and Development Program of China [2019YFE0129400]
- NFSC [81925035, 81521005]
- National Special Project for Significant New Drugs Development [2018ZX09711002-010-002]
- Shanghai SciTech Innovation Initiative [19431903100, 18430740800]
- Shanghai Collaborative Innovation Group of Early Diagnosis and Precise Treatment of Hemangiomas and Vascular Malformations [SSMU-ZDCX20180701]
- PIFI fellowship, CAS
The study demonstrated that the targeted delivery of CSF1R inhibitor using magnetic liposomes, along with magnetic hyperthermia, can remodel the tumor microenvironment, activate immune responses, and inhibit tumor growth and recurrence.
Background: Immunotherapy has profoundly changed the landscape of cancer management and represented the most significant breakthrough. Yet, it is a formidable challenge that the majority of cancers - the so-called cold tumors - poorly respond to immunotherapy. To find a general immunoregulatory modality that can be applied to a broad spectrum of cancers is an urgent need. Methods: Magnetic hyperthermia (MHT) possesses promise in cancer therapy. We develop a safe and effective therapeutic strategy by using magnetism-mediated targeting MHT-immunotherapy in cold colon cancer. A magnetic liposomal system modified with cell-penetrating TAT peptide was developed for targeted delivery of a CSF1R inhibitor (BLZ945), which can block the CSF1-CSF1R pathway and reduce M2 macrophages. The targeted delivery strategy is characterized by its magnetic navigation and TAT-promoting intratumoral penetration. Results: The liposomes (termed TAT-BLZmlips) can induce ICD and cause excessive CRT exposure on the cell surface, which transmits an eat-me signal to DCs to elicit immunity. The combination of MHT and BLZ945 can repolarize M2 macrophages in the tumor microenvironment to relieve immunosuppression, normalize the tumor blood vessels, and promote T-lymphocyte infiltration. The antitumor effector CD8(+) T cells were increased after treatment. Conclusion: This work demonstrated that TAT-BLZmlips with magnetic navigation and MHT can remodel tumor microenvironment and activate immune responses and memory, thus inhibiting tumor growth and recurrence.
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