Noninvasive delivery of oligonucleotide by penetratin-modified polyplexes to inhibit protein expression of intraocular tumor

Abstract

Our present study aimed to develop an antisense oligonucleotide (ASO) delivery system to achieve gene silencing in intraocular tumor via topical instillation. ASO specific for luciferase was chosen as model drug, polyamidoamine (PG5) was employed to condense ASO, and penetratin (Pene) was used to enhance cellular uptake. Nanoscale PG5/ASO/Pene polyplex was stabilized via noncovalent bonding. In vitro evaluations indicated that PG5/ASO/Pene exhibited improved cell-penetrating and gene silencing ability compared with naked ASO and PG5/ASO. Subcutaneous and orthotopic tumor models expressing luciferase were established in nude mice. After treated by PG5/ASO/Pene, immunohistochemical results of subcutaneous tumors showed significant inhibition of luciferase expression via peritumoral injection, and bioluminescence from orthotopic tumor was obviously weakened via topical instillation. To date, few works were successful in noninvasive treatment of intraocular diseases using antisense strategy, this penetratin-modified polyplex could be a promising vector to inhibit protein expression by effectively delivering ASOs into the eye.