Department of Molecular Therapeutics, Center for Food & Medical Innovation, Institute for the Promotion of Business-Regional Collaboration, Hokkaido University, North 8 West 5, Kita-ku, Sapporo 060-0808, Japan.
Department of Chemical Systems Engineering, School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
Int J Mol Sci. 2022 Jun 9;23(12):6457. doi: 10.3390/ijms23126457.
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, -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.
通过利用和免疫调节癌细胞独特的生物学特性，在癌症药物发现和靶向治疗方面可能取得重大进展。本综述总结了我们通过将黑色素生成底物 - 丙酰半胱氨酰苯酚（NPrCAP：酪氨酸的胺类似物）与磁铁矿纳米颗粒（MNP）缀合来开发新型化疗-热-免疫治疗（CTI 治疗）的努力。在我们的方法中，NPrCAP 因其选择性掺入黑色素瘤细胞而提供了独特的药物递送系统（DDS）。由于其产生的高反应性自由基（黑色素瘤靶向化疗），它也可用作黑色素瘤靶向治疗药物。此外，由于暴露于交变磁场（AMF）时 MNP 产生热量会导致热休克蛋白（HSP）表达，因此利用 MNP 是开发热免疫疗法的平台。这篇全面的综述涵盖了实验性体内和体外小鼠黑色素瘤模型以及对少数晚期黑色素瘤患者进行的初步临床试验，并讨论了 CTI 治疗的未来方向。
