Biocompatible micellar nanovectors achieve efficient gene transfer to vascular lesions without cytotoxicity and thrombus formation

Abstract

Gene therapy, a promising treatment for vascular disease, requires appropriate gene vectors with high gene transfer efficiency, good biocompatibility and low cytotoxicity. To satisfy these requirements from the approach of nonviral vectors, a novel block copolymer, poly

Impact of polyplex micelles installed with cyclic RGD peptide as ligand on gene delivery to vascular lesions

“…22,23 Our previous study indeed showed that administration of PEG-PAsp(DET) micelles into rabbit carotid artery accomplished appreciable gene transfer to the artery, without occlusion by thrombus formation. 20 In contrast, the same study revealed that polyplex made from polyethyleneimine markedly caused thrombus occlusion after intra-arterial application, indicating that positively charged polyplex potentially underwent aggregation with plasma proteins and blood cells. As thrombus formation possibly interferes with the process of gene transfer and further impairs vascular functions, it appears necessary for gene vectors for the treatment of vascular diseases to possess non-thrombogenic properties, like PEG-PAsp(DET) micelles.…”

“…The balloon was inflated at physiological pressure and passed through the common carotid artery three times with constant rotation. 20 At 21 days after balloon injury, polyplex micelles were administered into the common carotid artery, in which neointimal hyperplasia had been induced. pCAccluc+ was complexed with cRGD-PEG-PAsp(DET) or PEG-PAsp(DET) at N/P ratio of 5.…”

“…16,17 Because of the hydrophilic property of the PEG shell, the polyplex micelle minimizes nonspecific interactions with various bio-components, realizing high biocompatibility and stability in vivo. [18][19][20] In previous studies, we also designed PEG-block-polycation carrying ethylenediamine units (PEGPAsp(DET)) in the side chain and reported that polyplex micelles with PEG-PAsp(DET) accomplished appreciable gene transfer efficiency with low cytotoxicity. 20,21 After internalization of PEG-PAsp(DET) micelles into the intracellular compartment by endocytosis, the ethylenediamine units are expected to promote translocation of the polyplex micelles toward the cytoplasm due to endosomal membrane destabilization, resulting in improvement of gene transfer efficiency.…”

“…[18][19][20] In previous studies, we also designed PEG-block-polycation carrying ethylenediamine units (PEGPAsp(DET)) in the side chain and reported that polyplex micelles with PEG-PAsp(DET) accomplished appreciable gene transfer efficiency with low cytotoxicity. 20,21 After internalization of PEG-PAsp(DET) micelles into the intracellular compartment by endocytosis, the ethylenediamine units are expected to promote translocation of the polyplex micelles toward the cytoplasm due to endosomal membrane destabilization, resulting in improvement of gene transfer efficiency. 22,23 Furthermore, to increase cellular uptake of polyplex micelles, we recently attempted to introduce appropriate ligands into their surface.…”

A review of RGD-functionalized nonviral gene delivery vectors for cancer therapy

“…67,70,71 Polymeric micelles Polyplex micelles composed of PEG-polycation block copolymers and pDNA have been widely used as nonviral vectors with a potential for systemic applications. [72][73][74] The size of these polyplex micelles is B100 nm, which is considered to be optimal for systemic administration. Moreover, these polyplex micelles contain a biocompatible PEG shell layer, which prevents any sort of nonspecific interaction with blood components.…”