Zhuang Jialang, Zhang Jie, Wu Minhao, Zhang Yuanqing
Guangdong Key Laboratory of Chiral Molecule and Drug Discovery School of Pharmaceutical Sciences Sun Yat-sen University Guangzhou Guangdong 510006 P. R. China.
Department of Immunology Zhongshan School of Medicine Sun Yat-sen University 74 Zhongshan 2nd Road Guangzhou 510080 P. R. China.
Adv Sci (Weinh). 2019 Oct 4;6(22):1901462. doi: 10.1002/advs.201901462. eCollection 2019 Nov.
Nanomedicine has brought great advances for drug delivery by improving the safety and efficacy of pharmaceuticals. However, many nanomaterials showing good distribution property in vitro often display poor cellular uptake during in vivo administration. Current cellular uptake research models are mainly based on the traditional 2D culture system, which is a single layer and static system, thus the results cannot accurately reflect the distribution of nanoparticles (NPs) in vivo. In the present study, a multiple tumor culture chip (MTC-chip) is constructed to mimic solid tumor and dynamic fluid transport, in order to better study NPs penetration in vitro. Cellular uptake of mesoporous silica particles (MSNs) is evaluated using the 3D tumor spheroids on chip, and it is found that: 1) continuous administration results in larger MSNs penetration than transient administration at the same dose; 2) the size effect on cellular uptake is less significant than reported by previous in vitro studies; and 3) pretreatment with hyaluronidase (HAase) enhances the tumor penetration of large-size MSNs.
纳米医学通过提高药物的安全性和有效性，在药物递送方面取得了巨大进展。然而，许多在体外显示出良好分布特性的纳米材料在体内给药时往往表现出较差的细胞摄取。当前的细胞摄取研究模型主要基于传统的二维培养系统，这是一个单层且静态的系统，因此结果无法准确反映纳米颗粒（NPs）在体内的分布。在本研究中，构建了一种多肿瘤培养芯片（MTC芯片）来模拟实体瘤和动态流体运输，以便更好地研究纳米颗粒在体外的渗透。使用芯片上的三维肿瘤球体评估介孔二氧化硅颗粒（MSNs）的细胞摄取，发现：1）在相同剂量下，连续给药导致MSNs的渗透比瞬时给药更大；2）尺寸对细胞摄取的影响不如先前体外研究所报道的那么显著；3）用透明质酸酶（HAase）预处理可增强大尺寸MSNs的肿瘤渗透。
