In vivo Serum Enabled Production of Ultrafine Nanotherapeutics for Cancer Treatment.
In vivo Serum Enabled Production of Ultrafine Nanotherapeutics for Cancer Treatment.
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DOI：
10.1016/j.mattod.2020.03.005
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Mu Q;Lin G;Stephen ZR;Chung S;Wang H;Patton VK;Gebhart RN;Zhang M
用纳米载体全身递送疏水性抗癌药物，特别是用于耐药性和转移性癌症，仍然是一个挑战，因为难以实现高药物负载，同时在血液中保持小的流体动力学尺寸和胶体稳定性，以确保将有效量的药物递送至肿瘤细胞。在这里，我们介绍一种新的方法来应对这一挑战。在这种方法中，具有良好载药能力的较大尺寸的纳米纤维首先通过自组装过程构建，并且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，其继承了其母体纳米纤维的载药性质。我们证明了这种方法的有效性与临床可用的抗癌药物：紫杉醇（PTX）。在体外，载PTX的纳米颗粒进入癌细胞并诱导细胞凋亡。在体内，它们表现出延长的血液循环，不诱导全身毒性，并在侵袭性耐药乳腺癌和黑色素瘤的小鼠模型中显示出抑制肿瘤生长和转移的高效力。这项研究指出了一种改进抗癌药物输送和治疗的新策略。军需官和m. Z设想了该项目的各个方面。军需官进行了纳米纤维和纳米颗粒的合成和表征，体外和体内实验，数据收集和分析的所有实验。G. L.和V.K.协助材料合成和表征。G. L进行了体外和体内实验。z. R.美国，S. C，H。W.，和r. n. G.对材料的化学和形态特征进行了实验，并进行了数据分析。实验由Q. M.和m. z.与其他作者的投入。
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. Q.M. and M. Z conceived various aspects of the project. Q.M. performed all experiments on synthesis and characterize of nanofibers and nanoparticles, in vitro and in vivo experiments, data collection and analysis. G. L. and V. K. P. assisted on materials synthesis and characterization. G.L performed in vitro and in vivo experiments. Z. R. S., S. C, H. W., and R. N. G. performed experiments on chemical and morphological characterizations of materials and worked on data analysis. Experiments were designed and manuscripts were written by Q. M. and M. Z. with input from other authors.
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DOI：
10.1142/s1793962313500207
发表时间：
2013-12-01
影响因子：
1.2
作者：
Jiao, Song;Li, Wei;Yang, Ming
通讯作者：
Yang, Ming
影响因子：
5.1
作者：
CHMURNY, GN;HILTON, BD;BEUTLER, JA
通讯作者：
BEUTLER, JA
影响因子：
10.8
作者：
Crosasso, P;Ceruti, M;Cattel, L
通讯作者：
Cattel, L
影响因子：
4.3
作者：
Campos, Fernanda C.;Victorino, Vanessa J.;Cecchini, Rubens
通讯作者：
Cecchini, Rubens
粒径和表面电荷对聚合物纳米粒子的细胞摄取和生物分布的影响
影响因子：
14
作者：
He, Chunbai;Hu, Yiping;Yin, Chunhua
通讯作者：
Yin, Chunhua