Department of Biochemistry and Cell Biology, Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Department of Medical Oncology Laboratory, All India Institute of Medical Sciences, New Delhi 110029, India.
ACS Biomater Sci Eng. 2020 Sep 14;6(9):5024-5031. doi: 10.1021/acsbiomaterials.0c00599. Epub 2020 Aug 3.
Acquired drug resistance is a common occurrence and the main cause of melanoma treatment failure. Melanoma cells frequently developed resistance against cisplatin during chemotherapy, and thus, targeting delivery systems have been devised to decrease drug resistance, increase therapeutic efficacy, and reduce side effects. We genetically engineered a macromolecular carrier using the recursive directional ligation method that specifically targets cisplatin-resistant (Cis-R) melanoma. This carrier is composed of an elastin-like polypeptide (ELP) and multiple copies of Cis-R melanoma-targeting ligands (M-peptide). The designed ME contains 16 targeting ligands incorporated within an ELP and has an ideal thermal phase transition at 39 °C. When treated to melanoma cells, ME specifically accumulated in Cis-R B16F10 melanoma cells and accumulated to a lesser extent in parental B16F10 cells. Consistently, ME exhibited efficient homing and longer retention in tumor tissues in Cis-R melanoma-bearing mice than in parental B16F10 melanoma-bearing mice. Thus, ME was found to display considerable potential as a novel agent that specifically targets cisplatin-resistant melanoma.
获得性耐药是一种常见现象，也是黑色素瘤治疗失败的主要原因。黑色素瘤细胞在化疗过程中经常对顺铂产生耐药性，因此设计了靶向递药系统来降低耐药性、提高治疗效果和减少副作用。我们使用递归定向连接方法对一种大分子载体进行基因工程改造，该载体特异性靶向顺铂耐药（Cis-R）黑色素瘤。该载体由弹性蛋白样多肽（ELP）和多个 Cis-R 黑色素瘤靶向配体（M-肽）组成。设计的 ME 含有 16 个整合在 ELP 中的靶向配体，在 39°C 时具有理想的热相变。当用 ME 处理黑色素瘤细胞时，ME 特异性地在 Cis-R B16F10 黑色素瘤细胞中积累，而在亲本 B16F10 细胞中积累较少。一致地，ME 在 Cis-R 黑色素瘤荷瘤小鼠的肿瘤组织中表现出高效的归巢和更长的滞留时间，而在亲本 B16F10 黑色素瘤荷瘤小鼠中则较少。因此，ME 被发现具有作为一种新型靶向 Cis-R 黑色素瘤的药物的巨大潜力。
