Dual Receptor-Specific Peptides Modified Liposomes as VEGF siRNA Vector for Tumor-Targeting Therapy.

Dual Receptor-Specific Peptides Modified Liposomes as VEGF siRNA Vector for Tumor-Targeting Therapy. Curr Gene Ther. 2014 Jun 12; Authors: Yang Z, Xiang B, Dong D, Wang Z, Jingquan L, Xianrong Q Abstract Tumor angiogenesis involves multiple signaling pathways that provide potential therapeutic targets to inhibit tumor growth and metastasis. Regarding the significant role of vascular endothelial growth factor (VEGF) in angiogenesis and tumor progression, VEGF sequence-specific small interfering RNA (siRNA) for antiangiogenic tumor therapy are under development. In the present study, a dual-modified liposomes (At-Lp) was designed by attaching two receptor-specific peptides, i.e. low-density lipoprotein receptor-related protein receptor (Angiopep) for brain tumor targeting and neuropilin-1 receptor (tLyP-1) for tumor penetration. Gene transfection and silencing, and antitumor effect of the At-Lp loaded with VEGF siRNA was evaluated in vitro and in orthotopic xenograft models of U87 MG tumor. The At-Lp significantly enhanced cellular uptake (2-fold) and down-regulated expression of VEGF in U87 MG glioblastoma cells comparing with non-modified and single-modified liposomes. The internalization of the At-Lp into tumor cells was taken via receptor-mediated endocytosis, followed by an effective endosomal escape of loaded siRNA into the cytoplasm. The At-Lp showed great superiority in inhibition of tumor growth, antiangiogenesis, expression o...
Source: Current Gene Therapy - Category: Genetics & Stem Cells Authors: Tags: Curr Gene Ther Source Type: research