Transformative Nanomedicine of an Amphiphilic Camptothecin Prodrug for Long Circulation and High Tumor Uptake in Cancer Therapy
Transformative Nanomedicine of an Amphiphilic Camptothecin Prodrug for Long Circulation and High Tumor Uptake in Cancer Therapy
复制标题
两亲性喜树碱前药的转化纳米药物在癌症治疗中具有长循环和高肿瘤摄取作用
DOI：
10.1021/acsnano.7b03003
复制
发表时间：
2017-09-01
期刊：
影响因子：
17.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Zhang, Fuwu;Zhu, Guizhi;Chen, Xiaoyuan
我们报道了一种喜树碱（CPT）前药，它在溶液中配制良好，并在体内迅速转化为长循环的纳米复合物，用于高效的药物传递和有效的癌症治疗。具体来说，使用氧化还原反应的二硫连接体，CPT与白蛋白结合的埃文斯蓝（EB）衍生物结合；所得到的两亲性CPT-ss-EB前药在水溶液中自组装成纳米结构，从而具有高溶解度和稳定性。通过将CPT-ss-EB与内源性白蛋白结合，80 nm的CPT-ss-EB纳米颗粒迅速转化为7 nm的白蛋白/前药纳米复合物。CPT-ss- eb在癌细胞内有效递送，以氧化还原反应的方式释放完整的CPT，并表现出与CPT一样有效的细胞毒性。在小鼠中，白蛋白/CPT-ss- eb纳米复合物表现出明显的长血液循环（比CPT高130倍）和有效的肿瘤积累（比CPT高30倍），因此有助于良好的治疗效果。总的来说，这种变革性纳米医学的策略有望有效地给药。
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.