Polymeric Nanoparticles Controlled by On‐Chip Self‐Assembly Enhance Cancer Treatment Effectiveness,Advanced Healthcare Materials

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Polymeric Nanoparticles Controlled by On‐Chip Self‐Assembly Enhance Cancer Treatment Effectiveness
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-10-18 , DOI: 10.1002/adhm.202001633
Sungjin Jung _{1,

2} , Junseok Lee ₃ , Junha Lim ₃ , Jeeyeon Suh ₃ , Taeyoung Kim ₁ , Jungho Ahn ₁ , Won Jong Kim _{2,

3} , YongTae Kim _{1,

4,

5,

6}

Affiliation

Nanoparticle (NP)‐based drug delivery systems or nanomedicines have broadened the horizon of translational research for decades. Conventional bulk mixing synthesis methods have impeded successful clinical translations of nanomedicines due to the limited ability of the controlled, scalable production with high uniformity. Herein, an on‐chip preparation of self‐assembled, drug‐encapsulated polymeric NPs is presented for their improved uniformity and homogeneity that results in enhanced anti‐cancer effect in vitro and in vivo. The NPs are 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) exhibit narrower size distributions and better size tunability. It is found that the improved uniformity and homogeneity of the MVPs not only enhance cellular uptake and anti‐cancer effect with pH‐responsive drug release in vitro, but also result in an improved tumor regression and decreased side effects at off‐targeted organs in vivo. The findings demonstrate that uniformly designed NPs with more homogeneous properties can induce a significant enhancement of an anti‐cancer effect in vivo. The results show the potential of a high‐speed on‐chip synthesis as a scalable manufacturing platform for reliable clinical translations of nanomedicines.

中文翻译：

片上自组装控制的聚合物纳米颗粒增强癌症治疗效果

几十年来，基于纳米颗粒（NP）的药物输送系统或纳米药物拓宽了转化研究的视野。由于高均匀性的受控、可扩展生产的能力有限，传统的批量混合合成方法阻碍了纳米药物的成功临床转化。在此，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，从而增强了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，微涡合成纳米颗粒（MVP）表现出更窄的尺寸分布和更好的尺寸可调性。研究发现，MVP 均匀性和同质性的改善不仅可以增强细胞摄取和体外 pH 响应药物释放的抗癌作用，而且可以改善体内肿瘤消退并减少脱靶器官的副作用。研究结果表明，具有更均质特性的统一设计的纳米颗粒可以显着增强体内抗癌作用。结果显示了高速片上合成作为可扩展制造平台的潜力，可实现纳米药物的可靠临床转化。

更新日期：2020-11-18

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