We report a camptothecin (CPT) prodrug that was well formulated in solution and rapidly transformed into long-circulating nanocomplexes in vivo for highly efficient drug delivery and effective cancer therapy. Specifically, using a redox-responsive disulfide linker, CPT was conjugated with an albumin-binding Evans blue (EB) derivative; the resulting amphiphilic CPT-ss-EB prodrug self-assembled into nanostructures in aqueous solution, thus conferring high solubility and stability. By binding CPT-ss-EB to endogenous albumin, the 80 nm CPT-ss-EB nanoparticles rapidly transformed into 7 nm albumin/prodrug nanocomplexes. CPT-ss-EB was efficient at intracellular delivery into cancer cells, released intact CPT in a redox-responsive manner, and exhibited cytotoxicity as potent as CPT. In mice, the albumin/CPT-ss-EB nanocomplex exhibited remarkably long blood circulation (130-fold greater than CPT) and efficient tumor accumulation (30-fold of CPT), which consequently contributed to excellent therapeutic efficacy. Overall, this strategy of transformative nanomedicine is promising for efficient drug delivery.

中文翻译：

---

两性喜树碱前药的转化性纳米药物在癌症治疗中的长循环和高肿瘤摄取。

我们报道了一种喜树碱（CPT）前药，该药在溶液中配制良好，并在体内迅速转变成长循环的纳米复合物用于高效的药物输送和有效的癌症治疗。具体而言，使用氧化还原响应性二硫键，将CPT与结合白蛋白的伊文思蓝（EB）衍生物缀合。所得两亲性CPT-ss-EB前药在水溶液中自组装成纳米结构，因此具有较高的溶解度和稳定性。通过将CPT-ss-EB与内源性白蛋白结合，80 nm CPT-ss-EB纳米颗粒迅速转变为7 nm白蛋白/前药纳米复合物。CPT-ss-EB在细胞内递送到癌细胞中是有效的，以氧化还原响应方式释放完整的CPT，并显示出与CPT一样强的细胞毒性。在小鼠中，白蛋白/ CPT-ss-EB纳米复合物表现出非常长的血液循环（比CPT大130倍）和有效的肿瘤蓄积（CPT的30倍），因此有助于出色的治疗功效。总体而言，这种转化性纳米医学的策略有望有效地进行药物递送。