Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC₅₀ values of CD20-SA-NPs were reduced to 5.7 and 2.6 μg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg^-1·d^-1, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

中文翻译：

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带有抗CD20适体的沙利霉素负载脂质聚合物纳米颗粒可选择性抑制人CD20 +黑色素瘤干细胞。

黑色素瘤是最致命的皮肤癌类型。CD20 +黑色素瘤干细胞（CSC）对于黑色素瘤的转移和起始至关重要。因此，选择性消除CD20 +黑色素瘤CSC代表了根除黑色素瘤的有效治疗方法。沙利霉素已成为针对各种CSC的有效药物。由于其不良的溶解性，从未评估过其对黑素瘤CSCs的治疗功效。为了靶向CD20 +黑色素瘤CSC，我们设计了带有抗CD20适体（CD20-SA-NPs）的负载沙利霉素的脂质聚合物纳米颗粒。使用一步纳米沉淀法，制备了载有盐霉素的脂质聚合物纳米颗粒（SA-NPs），然后通过马来酰亚胺-硫醇反应将硫醇化抗CD20适体与SA-NP缀合获得CD20-SA-NP。CD20-SA-NP的尺寸小至96.3 nm，包封率高于60％，并具有持续的药物释放能力。CD20 +黑色素瘤CSC对CD20-SA-NP的吸收显着高于SA-NP和沙利霉素的吸收，从而导致体外细胞毒性作用大大增强，因此，IC在A375 CD + 20细胞和WM266-4 CD +细胞中，CD20-SA-NPs的_50个值分别降至5.7和2.6μg/ mL。CD20-SA-NPs对CD20 +黑色素瘤CSCs具有选择性的细胞毒性，这在抑制肿瘤球的形成和抑制黑色素瘤细胞系中CD20 +细胞的比例方面具有最佳的治疗效果证明了这一点。在具有黑素瘤异种移植物的小鼠中，与SA-NPs和沙利霉素相比，给予CD20-SA-NPs（沙利霉素5 mg·kg ^-1 ·d ^-1，静脉注射60 d）显示出更好的抑制黑素瘤生长的功效。总之，CD20是向黑色素瘤CSC输送药物的绝佳靶标。CD20-SA-NPs可将盐霉素有效递送至CD20 +黑色素瘤CSC，代表了一种有前途的黑色素瘤治疗方法。