4.7 Review

Immunomodulation of Melanoma by Chemo-Thermo-Immunotherapy Using Conjugates of Melanogenesis Substrate NPrCAP and Magnetite Nanoparticles: A Review

Journal

Publisher

MDPI
DOI: 10.3390/ijms23126457

Keywords

melanoma; chemo-thermo-immunotherapy; melanogenesis; magnetite nanoparticle; drug delivery system; heat shock protein; in situ vaccine therapy; immune checkpoint inhibitor

Funding

  1. Ministry of Health, Labour and Welfare of Japan [H21-Nano-006]

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This review summarizes the development of a novel chemo-thermo-immunotherapy (CTI therapy) that exploits the unique biological properties of cancer cells. The authors have successfully conjugated a melanogenesis substrate with magnetite nanoparticles, providing a selective drug delivery system for melanoma cells. This approach combines targeted chemotherapy with thermo-immunotherapy, showing promising results in mouse models and limited clinical trials on advanced melanoma patients.
A major advance in drug discovery and targeted therapy directed at cancer cells may be achieved by the exploitation and immunomodulation of their unique biological properties. This review summarizes our efforts to develop novel chemo-thermo-immunotherapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine), with magnetite nanoparticles (MNP). In our approach, NPrCAP provides a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It also functions as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Moreover, the utilization of MNP is a platform to develop thermo-immunotherapy because of heat shock protein (HSP) expression upon heat generation in MNP by exposure to an alternating magnetic field (AMF). This comprehensive review covers experimental in vivo and in vitro mouse melanoma models and preliminary clinical trials with a limited number of advanced melanoma patients. We also discuss the future directions of CTI therapy.

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