Abstract 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.

中文翻译：

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体内血清能够生产用于癌症治疗的超细纳米药物

摘要：利用纳米载体全身递送疏水性抗癌药物，尤其是耐药性和转移性癌症，仍然是一个挑战，因为难以实现高载药量，同时保持较小的流体动力学尺寸和血液中的胶体稳定性，以确保药物的递送。对肿瘤细胞有效量的药物。在这里，我们介绍一种新方法来应对这一挑战。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的纳米纤维，并在血管内注射并与体内血清蛋白相互作用后，这些纳米纤维分解成较小尺寸的超细纳米颗粒，继承了来自其母体纳米纤维的载药特性。我们用临床上可用的抗癌药物紫杉醇（PTX）证明了这种方法的功效。在体外，负载 PTX 的纳米粒子进入癌细胞并诱导细胞凋亡。在体内，它们在血液中的循环时间延长，不会引起全身毒性，并且在侵袭性、耐药性乳腺癌和黑色素瘤小鼠模型中显示出高效抑制肿瘤生长和转移的功效。这项研究提出了一种改善抗癌药物输送和治疗的新策略。