Microfluidics‐enabled Serial Assembly of Lipid‐siRNA‐sorafenib Nanoparticles for Synergetic Hepatocellular Carcinoma Therapy

• DOI: 10.1002/adma.202209672
• Publication Date: 2023-02-07T22:18:19Z
• Authors: Yao Chen; Dong Zhao; Feng Xiao; Xuanyu Li; Jia'an Li; Zhenwei Su; Xingyu Jiang
• Keywords: Mice; Carcinoma, Hepatocellular; Cell Line, Tumor; Microfluidics; Liver Neoplasms; Humans; Animals; Nanoparticles; Sorafenib; RNA, Small Interfering; Lipids

Abstract 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 assembly processes mNPs. Here microfluidics‐enabled serial (MESA) mNPs presented. The microfluidic chip, as mini‐conveyor initial materials, sequentially enables sorafenib supramolecule, electrostatic adsorption siRNA, surface protective lipids. produced lipid‐siRNA‐sorafenib (LSS NPs) have ultrahigh encapsulation efficiencies (≈100%) siRNA (≈95%), which benefit from accommodation both fast slow on chip. Although carrying negative charges, LSS NPs enable cytosolic delivery agents high gene silencing efficiency within tumor cells. In vivo, delivering hypoxia‐induced factor (HIF1α)‐targeted efficiently regress tumors Hep3B xenograft hepatocellular carcinoma patient‐derived primary cells (PDCX) finally extend average survival PDCX mice 68 days. Thus, this strategy promising sorafenib/siRNA combination therapy, MESA can be universal platform fabricating complex nanosystems.