Polymeric Nanoparticles Controlled by On-Chip Self-Assembly Enhance Cancer Treatment Effectiveness.
Polymeric Nanoparticles Controlled by On-Chip Self-Assembly Enhance Cancer Treatment Effectiveness.
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芯片上自组装控制的聚合物纳米颗粒提高癌症治疗效果。
DOI：
10.1002/adhm.202001633
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发表时间：
2020-11
影响因子：
10
通讯作者：
Kim Y
中科院分区：
文献类型：
--
作者：
Jung S;Lee J;Lim J;Suh J;Kim T;Ahn J;Kim WJ;Kim Y
数十年来，基于纳米颗粒（NP）的药物输送系统拓宽了我们的转化研究视野。然而，由于高均匀性纳米药物的受控、可扩展生产能力有限，传统的批量混合方法阻碍了纳米药物的成功临床转化。在此，我们提出了一种自组装、药物封装的聚合物纳米颗粒的芯片制备方法，其均匀性和同质性得到改善，与本体合成相比，可增强体外和体内的抗癌效果。纳米颗粒是通过在旋转微涡流反应器 (SMR) 中快速对流混合亲水性聚合物和抗癌药物阿霉素 (DOX) 的两种水溶液来配制的。与传统的本体混合纳米颗粒（BMP）相比，微涡流合成的纳米颗粒（MVP）表现出更窄的尺寸分布和更好的尺寸可调性以及不同的雷诺数。所生产的 MVP 的均匀性和同质性得到改善，增强了细胞摄取和抗癌效果，并在体外实现 pH 响应性药物释放。此外，MVP 在荷瘤小鼠模型中的治疗应用在肿瘤区域呈现出更高的积累，从而改善了肿瘤消退并减少了非靶器官的副作用。我们的研究结果表明，具有更均匀特性的统一设计的纳米颗粒可以显着增强体内抗癌作用。我们相信，我们对纳米颗粒增强治疗效果和改善均匀性之间相关性的验证可以提供高速片上合成的潜力，作为可扩展的制造平台，实现纳米药物的可靠临床转化。通过片上自组装可以轻松制备均匀且均质的药物封装聚合物纳米粒子（NP）。与散装混合纳米颗粒 (BMP) 相比，微涡流合成的纳米颗粒 (MVP) 在细胞摄取和抗癌作用方面表现出优异的特性。特别是，MVP 在肿瘤区域表现出高积累，并在荷瘤小鼠模型中增强肿瘤消退，呈现出可重复制备纳米药物以实现可靠临床转化的潜力。
Nanoparticle (NP) based drug delivery systems have broadened our horizon of translational research for decades. However, conventional bulk mixing methods have impeded successful clinical translations of nanomedicines due to the limited ability of controlled, scalable production of nanomedicines with high uniformity. Herein, we present an on-chip preparation of self-assembled, drug-encapsulated polymeric NPs for their improved uniformity and homogeneity, leading to enhanced anti-cancer effect in vitro and in vivo compared to bulk synthesis. The NPs were formulated through rapid convective mixing of two aqueous solutions of a hydrophilic polymer and an anti-cancer drug, doxorubicin (DOX), in the swirling microvortex reactor (SMR). Compared to conventional bulk-mixed NPs (BMPs), the microvortex-synthesized NPs (MVPs) exhibited narrower size distributions and better size tunability with varied Reynolds numbers. The improved uniformity and homogeneity of the produced MVPs enhanced cellular uptake and anti-cancer effect with pH-responsive drug release in vitro. Furthermore, therapeutic application of MVPs in tumor-bearing mice models presented much higher accumulation at the tumor region, resulting in an improved tumor regression and decreased side effects at off-targeted organs. Our findings suggest that uniformly designed NPs with more homogeneous properties can induce a significant enhancement of an anti-cancer effect in vivo. We believe that our validation of the correlation between an enhanced therapeutic effect and improved uniformity of NPs can provide the potential of a high-speed on-chip synthesis as a scalable manufacturing platform for reliable clinical translations of nanomedicines. Facile preparation of uniform and homogenous drug-encapsulated polymeric nanoparticles (NPs) is achieved with on-chip self-assembly. The microvortex-synthesized NPs (MVPs) demonstrate superior properties in cellular uptake and anti-cancer effect compared to bulk mixed NPs (BMPs). In particular, the MVPs exhibit high accumulation at tumor region and enhanced tumor regression in tumor-bearing mouse model, presenting potential of reproducible preparation of nanomedicines for reliable clinical translation.
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影响因子：
46.2
作者：
Behzadi S;Serpooshan V;Tao W;Hamaly MA;Alkawareek MY;Dreaden EC;Brown D;Alkilany AM;Farokhzad OC;Mahmoudi M
通讯作者：
Mahmoudi M
影响因子：
3.5
作者：
Damiati S;Kompella UB;Damiati SA;Kodzius R
通讯作者：
Kodzius R
影响因子：
19
作者：
Liu, Dongfei;Bernuz, Cristina Rodriguez;Santos, Helder A.
通讯作者：
Santos, Helder A.
影响因子：
19
作者：
Majedi, Fatemeh Sadat;Hasani-Sadrabadi, Mohammad Mahdi;Renaud, Philippe
通讯作者：
Renaud, Philippe
影响因子：
4.9
作者：
Li, Shyh-Dar;Huang, Leaf
通讯作者：
Huang, Leaf