Mu Qingxin, Lin Guanyou, Stephen Zachary R, Chung Steve, Wang Hui, Patton Victoria K, Gebhart Rachel N, Zhang Miqin
Department of Materials Science and Engineering, University of Washington, Seattle, Washington, 98195, USA.
Department of Chemical Engineering, University of Washington, Seattle, Washington, 98195, USA.
Mater Today (Kidlington). 2020 Sep;38:10-23. doi: 10.1016/j.mattod.2020.03.005. Epub 2020 May 4.
Systemic delivery of hydrophobic anti-cancer drugs with nanocarriers, particularly for drug-resistant and metastatic cancer, remain a challenge because of the difficulty to achieve high drug loading, while maintaining a small hydrodynamic size and colloid stability in blood to ensure delivery of an efficacious amount of drug to tumor cells. Here we introduce a new approach to address this challenge. In this approach, nanofibers of larger size with good drug loading capacity are first constructed by a self-assembly process, and upon intravascular injection and interacting with serum proteins in vivo, these nanofibers break down into ultra-fine nanoparticles of smaller size that inherit the drug loading property from their parent nanofibers. We demonstrate the efficacy of this approach with a clinically available anti-cancer drug: paclitaxel (PTX). In vitro, the PTX-loaded nanoparticles enter cancer cells and induce cellular apoptosis. In vivo, they demonstrate prolonged circulation in blood, induce no systemic toxicity, and show high potency in inhibiting tumor growth and metastasis in both mouse models of aggressive, drug-resistant breast cancer and melanoma. This study points to a new strategy toward improved anti-cancer drug delivery and therapy.
利用纳米载体进行疏水性抗癌药物的全身递送，尤其是针对耐药性和转移性癌症，仍然是一项挑战，因为难以实现高载药量，同时还要在血液中保持较小的流体动力学尺寸和胶体稳定性，以确保将有效剂量的药物递送至肿瘤细胞。在此，我们介绍一种应对这一挑战的新方法。在该方法中，首先通过自组装过程构建具有良好载药能力的较大尺寸纳米纤维，在血管内注射并与体内血清蛋白相互作用后，这些纳米纤维分解为尺寸更小的超细纳米颗粒，这些纳米颗粒继承了其母体纳米纤维的载药特性。我们用一种临床可用的抗癌药物紫杉醇（PTX）证明了该方法的有效性。在体外，负载PTX的纳米颗粒进入癌细胞并诱导细胞凋亡。在体内，它们在血液中循环时间延长，不产生全身毒性，并且在侵袭性、耐药性乳腺癌和黑色素瘤的小鼠模型中均显示出高效抑制肿瘤生长和转移的能力。这项研究指出了一种改善抗癌药物递送和治疗的新策略。
