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

Chen, Yao1; Zhao, Dong2,3; Xiao, Feng1; Li, Xuanyu1; Li, Jia'an1; Su, Zhenwei1; Jiang, Xingyu1

2023-02-01

10.1002/adma.202209672

ADVANCED MATERIALS   Impact Factor & Quartile

0935-9648

1521-4095

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 (approximate to 100%) and siRNA (approximate to 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 (HIF1 alpha)-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.

hepatocellular carcinoma nanoparticle assembly serial microfluidics siRNA delivery sorafenib

SCI

English

NI Journal Papers

First ; Corresponding

National Key R&D Program of China["2020YFA0908900","2018YFA0902600","2022YFB3804700","2021YFF1200100","2021YFF1200800"] ; Shenzhen Key Laboratory of Smart Healthcare Engineering[ZDSYS20200811144003009] ; National Natural Science Foundation of China["22234004","22104050","81730051"] ; Guangdong Provincial Key Laboratory of Advanced Biomaterials[2022B1212010003] ; Guangdong Innovative and Entrepreneurial Research Team Program[2019ZT08Y191] ; Shenzhen Bay Laboratory[SZBL2019062801004]

Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics

Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter

WOS:000934561800001

WILEY-V C H VERLAG GMBH

MATERIALS SCIENCE

Web of Science

1.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen Key Lab Smart Healthcare Engn, Guangdong Prov Key Lab Adv Biomat, Shenzhen 518055, Guangdong, Peoples R China
2.Southern Univ Sci & Technol Shenzhen, Shenzhen Third Peoples Hosp, Div Liver Surg, Affiliated Hosp 2, Guangdong 518112, Peoples R China
3.Southern Univ Sci & Technol Shenzhen, Shenzhen Third Peoples Hosp, Organ Transplantat Ctr, Affiliated Hosp 2, Guangdong 518112, Peoples R China

Chen, Yao,Zhao, Dong,Xiao, Feng,et al. Microfluidics-enabled Serial Assembly of Lipid-siRNA-sorafenib Nanoparticles for Synergetic Hepatocellular Carcinoma Therapy[J]. ADVANCED MATERIALS,2023.

Chen, Yao.,Zhao, Dong.,Xiao, Feng.,Li, Xuanyu.,Li, Jia'an.,...&Jiang, Xingyu.(2023).Microfluidics-enabled Serial Assembly of Lipid-siRNA-sorafenib Nanoparticles for Synergetic Hepatocellular Carcinoma Therapy.ADVANCED MATERIALS.

Chen, Yao,et al."Microfluidics-enabled Serial Assembly of Lipid-siRNA-sorafenib Nanoparticles for Synergetic Hepatocellular Carcinoma Therapy".ADVANCED MATERIALS (2023).