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 M₁₆E₁₀₈ contains 16 targeting ligands incorporated within an ELP and has an ideal thermal phase transition at 39 °C. When treated to melanoma cells, M₁₆E₁₀₈ specifically accumulated in Cis-R B16F10 melanoma cells and accumulated to a lesser extent in parental B16F10 cells. Consistently, M₁₆E₁₀₈ exhibited efficient homing and longer retention in tumor tissues in Cis-R melanoma-bearing mice than in parental B16F10 melanoma-bearing mice. Thus, M₁₆E₁₀₈ was found to display considerable potential as a novel agent that specifically targets cisplatin-resistant melanoma.

中文翻译：

---

靶向顺铂耐药的黑色素瘤使用呈现弹性蛋白样多肽的多价配体。

获得性耐药是黑色素瘤治疗失败的普遍现象和主要原因。黑色素瘤细胞在化疗期间经常发展出对顺铂的耐药性，因此，已经设计出靶向递送系统以降低耐药性，提高治疗效果并减少副作用。我们使用递归定向连接方法，专门针对顺铂耐药性（Cis-R）黑色素瘤的基因工程大分子载体。该载体由弹性蛋白样多肽（ELP）和顺式R-黑色素瘤靶向配体（M-肽）的多个副本组成。设计的M ₁₆ E ₁₀₈包含在ELP内的16个靶向配体，在39°C时具有理想的热相变。当治疗黑素瘤细胞时，M₁₆ E ₁₀₈特异性地积累在Cis-R B16F10黑色素瘤细胞中，而较少程度地积累在亲本B16F10细胞中。一致地，与具有亲本的B16F10黑色素瘤的小鼠相比，在具有Cis-R黑色素瘤的小鼠中，M ₁₆ E ₁₀₈在肿瘤组织中表现出有效的归巢和更长的保留。因此，发现M ₁₆ E ₁₀₈作为特异性靶向顺铂耐药性黑色素瘤的新型药物显示出相当大的潜力。