Lung cancer, with its high mortality and increasing morbidity, has become one of the most lethal malignancies worldwide. Here, we developed cyclic RGD peptide-directed and disulfide-crosslinked polymersomal doxorubicin (cRGD-PS-Dox) as a targeted chemotherapy for human non-small cell lung cancer (NSCLC). Notably, cRGD-PS-Dox exhibited a high Dox loading (15.2 wt.%), small hydrodynamic diameter (96 nm), superb stability, prominent targetability to α_vβ₃ integrin overexpressing A549 human lung cancer cells, and rapid release of the drug into nuclei, leading to a significantly improved antitumor activity compared with the control groups, i.e., PS-Dox and Lipo-Dox (a liposome injection employed in clinical settings). The pharmacokinetic and biodistribution results for cRGD-PS-Dox revealed similar elimination half-lives but two-fold enhanced tumor accumulation compared with PS-Dox and Lipo-Dox. Intriguingly, cRGD-PS-Dox effectively suppressed the growth of A549 lung tumors in both subcutaneous and orthotopic models with minimal adverse effects at a Dox dose of 12 mg/kg, leading to significant survival benefits compared with PS-Dox and Lipo-Dox. This α_vβ₃ integrin-targeting multifunctional polymersomal doxorubicin is highly promising for targeted chemotherapy of human NSCLC.

肺癌具有高死亡率和高发病率，已成为全世界最致命的恶性肿瘤之一。在这里，我们开发了环状RGD肽定向和二硫键交联的多柔比星阿霉素（cRGD-PS-Dox）作为人类非小细胞肺癌（NSCLC）的靶向化疗药物。值得注意的是，的cRGD-PS-Dox的显示出高的Dox装载（15.2重量％），小流体动力学直径（96纳米），极好的稳定性，靶向性突出到α _v β ₃与对照组，即PS-Dox和Lipo-Dox（在临床环境中使用的脂质体注射）相比，整合素过表达A549人肺癌细胞，并且药物迅速释放到细胞核中，从而导致抗肿瘤活性显着提高。与PS-Dox和Lipo-Dox相比，cRGD-PS-Dox的药代动力学和生物分布结果显示相似的消除半衰期，但肿瘤积累增加了两倍。有趣的是，cRGD-PS-Dox在皮下和原位模型中均能有效抑制A549肺肿瘤的生长，且Dox剂量为12 mg / kg时不良反应极小，与PS-Dox和Lipo-Dox相比，可显着提高生存率。此α _v β ₃ 靶向整联蛋白的多功能多柔比星阿霉素对人NSCLC的靶向化疗具有高度前景。