黑色素瘤,最具破坏性的皮肤癌之一，目前缺乏有效的临床治疗方法。递送功能基因以调节特定蛋白质表达以诱导黑素瘤细胞凋亡可能是有希望的治疗方法。然而,使用非病毒方法转染黑色素瘤细胞，特别是阳离子聚合物，提出了重大挑战。在这项研究中,我们合成了三个支化聚（β-氨基酯）（HPAEs），具有均匀分布的分支单元，但通过两步“低聚物组合”策略改变了空间长度。独特的拓扑结构使得HPAEs能够凝聚DNA以形成具有有利的物理化学性质的纳米大小的复合物。值得注意的是,HPAEs,特别是具有中间分支单元空间长度的HPAE-2，与领先的商业基因转染试剂相比，基因转染效率显着提高，jetprime,在人类黑色素瘤细胞中。此外，HPAE-2有效地将编码Bax的质粒传递到黑色素瘤细胞中，导致明显的促凋亡作用，而不会引起明显的细胞毒性。本研究通过利用分支单位的分布建立了一个有效的非病毒平台，用于黑色素瘤细胞的基因转染。为基因治疗在黑色素瘤治疗中的潜在临床应用铺平了道路。
Melanoma, one of the most devastating forms of skin cancer, currently lacks effective clinical treatments. Delivery of functional genes to modulate specific protein expression to induce melanoma cell apoptosis could be a promising therapeutic approach. However, transfecting melanoma cells using non-viral methods, particularly with cationic polymers, presents significant challenges. In this study, we synthesized three branched poly(β-amino ester)s (HPAEs) with evenly distributed branching units but varying space lengths through a two-step \"oligomer combination\" strategy. The unique topological structure enables HPAEs to condense DNA to form nano-sized polyplexes with favorable physiochemical properties. Notably, HPAEs, especially HPAE-2 with intermediate branching unit space length, demonstrated significantly higher gene transfection efficiency than the leading commercial gene transfection reagent, jetPRIME, in human melanoma cells. Furthermore, HPAE-2 efficiently delivered the Bax-encoding plasmid into melanoma cells, leading to a pronounced pro-apoptotic effect without causing noticeable cytotoxicity. This study establishes a potent non-viral platform for gene transfection of melanoma cells by harnessing the distribution of branching units, paving the way for potential clinical applications of gene therapy in melanoma treatment.
