Platelet membrane biomimetic nanoparticles for lung-targeted gene delivery:construction and targeting evaluation
WU Hongyan
HUI Wenting
QIAO Sai
LIU Miao
JI Qifeng
ZHOU Siyuan
LIU Daozhou
Abstract：Objective To construct platelet membrane biomimetic nanoparticles loaded with siHIF-1α and PSS31 for efficient treatment of hypoxic pulmonary hypertension.Methods The lung-targeted biomimetic nanoparticles siHIF-1α/PSS31 and siHIF-1α/PSS31@PM were prepared using electrostatic adsorption and extrusion methods.Their particle size,zeta potential,morphology,and stability were characterized by laser particle size analyzer,transmission electron microscopy,and gel electrophoresis.In vitro biocompatibility was evaluated through hemolysis and cytotoxicity assays.The uptake efficiency of siHIF-1α/PSS31 and siHIF-1α/PSS31@PM by normoxic and hypoxically damaged pulmonary microvascular endothelial cells(PMVECs)and pulmonary artery smooth muscle cells(PASMCs)was assessed using flow cytometry.In vivo targeting ability was investigated via live imaging and immunofluorescence staining experiments.Results The cationic polymer PSS31 efficiently encapsulated siHIF-1α.siHIF-1α/PSS31@PM exhibited a spherical morphology with a distinct core-shell structure and an average particle size of approximately(180.6±0.5)nm,showing no significant change in size over a period of 6 d.Besides,siHIF-1α/PSS31@PM showed no obvious hemolysis phenomenon and had no significant effect on the cell viability of PMVECs and PASMCs.Furthermore,siHIF-1α/PSS31@PM effectively targeted hypoxia-injured lung tissue and accumulated in PMVECs and PASMCs,with significantly better targeting efficiency than siHIF-1α/PSS31(P＜0.05).Conclusion siHIF-1α/PSS31@PM demonstrates highly efficient targeting of hypoxically damaged PMVECs and PASMCs,thereby offering a novel strategy for the pulmonary-targeted delivery of gene-based therapeutics.
Keywords：biomimetic gene delivery carrierplatelet membranecationic polymerhypoxia-inducible factor-1 alphasmall interfering RNAhypoxic pulmonary hypertensionlung-targeted drug delivery systemextrahepatic gene delivery
Publication Date：2026-07-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：8( 985-992 )