Enhanced intracellular and intranuclear drug delivery mediated by biomimetic peptide SVS-1 for anticancer therapy

Publication date: Available online 5 September 2019Source: International Journal of PharmaceuticsAuthor(s): Yucheng Xiang, Liqiang Chen, Rui Zhou, Yuan HuangAbstractTumor cell nucleus is the ultimate target of many first-line chemotherapeutics and therapeutic genes. However, nuclear drug delivery is always hampered by multiple intracellular obstacles especially low efficiency of cellular uptake and insufficient nuclear trafficking. It is urgent to establish novel nuclear drug delivery systems to simultaneously overcome barriers including cell membranes and nuclear envelope. Herein, an N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-based drug delivery system was designed to achieve enhanced intracellular and intranuclear drug delivery. A biomimetic peptide (SVS-1), derived from antimicrobial peptides, which was reported to efficiently penetrate cell membranes and translocate rapidly into nucleus without decreasing cell viability, was conjugated to the HPMA copolymer backbone. The in vitro studies showed that SVS-1 could enhance the uptake and nuclei accumulation of HPMA copolymer by 4.1 and 7.0-fold on human cervical cancer cells (HeLa) separately compared with corresponding non-SVS-1 modified HPMA copolymers (P-DOX). This also transferred to greater DNA damage, more apoptosis and superior cytotoxicity (2.4-fold) of doxorubicin which was chosen as the model drug and attached to SVS-1 modified HPMA copolymer (SVS-1-P-DOX). Furthermore, the in vivo investigation revealed that...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research