Smart nanoparticles assembled by endogenous molecules for siRNA delivery and Cancer therapy via CD44 and EGFR dual-targeting

Publication date: Available online 21 October 2018Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Yaoyao Liang, Jiahui Peng, Ning Li, Cynthia Yu-Wai-Man, Qian Wang, Yuhong Xu, Hongxia Wang, Aristides D Tagalakis, Zixiu DuAbstractWe developed an anticancer siRNA delivery system (named HLPR) through modular assembly of endogenous molecules. The structure of HLPR was a tightly condensed siRNA-peptide inner core in turn surrounded by the disordered lipid layer and thin HA coating from which the EGFR-targeted amino acid sequences of IVNQPTYGYWHY partially protrude outside of cell surfaces. Both HA and IVNQPTYGYWHY anchored on HLPR were responsible for targeting CD44 and EGFR overexpressed on the tumor cell surfaces, respectively. HLPR was relatively stable in the blood circulation and reached at the tumor tissue in vivo through passive and active targeting. Then HLPR entered tumor cells mainly through EGFR-mediated pathway followed by the separation of HA from the remaining parts of nanocomplexes. The HA-uncoated complexes escaped the endosome through the membrane fusion function of DOPE and released cargoes (siRNA and peptide/siRNA) in the cytoplasm. HLPR significantly inhibited the growth of implanted subcutaneous liver tumors without toxicity.Graphical Abstract

Source: Nanomedicine: Nanotechnology, Biology and Medicine - October 21, 2018 Category: Nanotechnology Source Type: research