Targeted delivery of anti-VEGF siRNAs by means of nucleopeptide complexes in a rat model of endometriosis

Abstract

Introduction. Gene therapy is an approach to the treatment of hereditary and multifactorial diseases by delivering nucleic acids into cells. Currently, its prospects for the treatment of endometriosis (EM), a common gynecological disease, have been shown. Gene therapy of EM is possible by inhibiting neoangiogenesis in endometrioid foci by suppressing VEGFA gene expression using RNA interference.
Aim: evaluation of the properties of electrostatically stabilized nucleopeptide complexes as delivery vehicles for anti-VEGF siRNAs in vitro and in rats with surgically induced endometriosis.
Methods. Physicochemical (size, charge, stability), toxic (resazurin test), and transfection (suppression of GFP gene expression) triple complexes of siRNA with arginine-cysteine-rich peptide carrier R6p coated with glutamate-rich polypeptide E6pH-CDP with a ligand to the CXCR4 receptor were studied. A subcutaneous EM model in Wistar rats was used for in vivo experiments.
Results. It has been demonstrated that the developed complexes are non-toxic, resistant to blood serum, and can ensure the delivery of siRNAs to endometrioid foci, stopping their growth.
Conclusions. The results obtained indicate the promise of the R6p/E6pH-CDP carrier modified with a CXCR4 receptor ligand for use as a delivery vehicle for anti-VEGF miRNAs in order to suppress angiogenesis in EM.