Chen Yao, Zhao Dong, Xiao Feng, Li Xuanyu, Li Jia'an, Su Zhenwei, Jiang Xingyu
Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, P.R. China.
Division of Liver Surgery and Organ Transplantation Center, Shenzhen Third People's Hospital, Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, 518112, P.R. China.
Adv Mater. 2023 Mar;35(13):e2209672. doi: 10.1002/adma.202209672. Epub 2023 Feb 17.
Multi-component nanoparticles (mNPs) hold great potential for disease prevention and treatment. However, a major barrier is the lack of versatile platforms to accommodate steps of assembly processes of mNPs. Here the microfluidics-enabled serial assembly (MESA) of mNPs is presented. The microfluidic chip, as a mini-conveyor of initial materials, sequentially enables the assembly of sorafenib supramolecule, electrostatic adsorption of siRNA, and surface assembly of protective lipids. The produced lipid-siRNA-sorafenib nanoparticles (LSS NPs) have ultrahigh encapsulation efficiencies for sorafenib (≈100%) and siRNA (≈95%), which benefit from the accommodation of both fast and slow processes on the chip. Although carrying negative charges, LSS NPs enable cytosolic delivery of agents and high gene silencing efficiency within tumor cells. In vivo, the LSS NPs delivering hypoxia-induced factor (HIF1α)-targeted siRNA efficiently regress tumors of Hep3B xenograft and hepatocellular carcinoma patient-derived primary cells xenograft (PDCX) and finally extend the average survival of PDCX mice to 68 days. Thus, this strategy is promising as a sorafenib/siRNA combination therapy, and MESA can be a universal platform for fabricating complex nanosystems.
多组分纳米颗粒（mNPs）在疾病预防和治疗方面具有巨大潜力。然而，一个主要障碍是缺乏通用平台来容纳mNPs组装过程的各个步骤。本文介绍了基于微流控的mNPs串联组装（MESA）。微流控芯片作为初始材料的微型输送器，依次实现了索拉非尼超分子的组装、siRNA的静电吸附以及保护性脂质的表面组装。所制备的脂质-siRNA-索拉非尼纳米颗粒（LSS NPs）对索拉非尼（≈100%）和siRNA（≈95%）具有超高的包封效率，这得益于芯片上对快速和慢速过程的兼容。尽管LSS NPs带负电荷，但它们能够实现药物的胞质递送并在肿瘤细胞内具有高基因沉默效率。在体内，递送靶向缺氧诱导因子（HIF1α）的siRNA的LSS NPs能有效使Hep3B异种移植瘤和肝癌患者来源的原代细胞异种移植瘤（PDCX）消退，并最终将PDCX小鼠的平均生存期延长至68天。因此，这种策略作为索拉非尼/ siRNA联合疗法具有广阔前景，并且MESA可成为制备复杂纳米系统的通用平台。
