Conjugates for Angiogenesis Targeted Gene Therapy

Compound

Gene

Target

Tumor Model

Reference c(RGD)-PEG-PEI

RGD4C-PEG-PEI

Pronectin F+®

RGDC-PEG-PEI

RGD-PEI

RGD-PEG-PEI

RGD-lipid nanoparticles siRNA

sFlt-1

LacZ

aVb3 integrin N2A neuroblastoma aVb3 integrin Human skin capillary endothelial cells aVb3 integrin Murine meth-AR-1 fibrosarcoma aVb3 integrin Mewo human melanoma aVb3 integrin Human cervical carcinoma aVb3 integrin Not reported aVb3 integrin CT26 human colon carcinoma aVb3 integrin PO2 human colon carcinoma

164 173 168 169 172

165 204

Luciferase Plasmid DNA

DNA Raf-1

RGD4C-PEG-cholesterol liposome CAT

was significant inhibition of tumor angiogenesis, reduced tumor growth rate, and a marked reduction of peritumoral vascularization.170 In another study, Kim et al. reported an anti-angiogen-esis strategy to block VEGF receptor function and thereby inhibit endothelial cell proliferation.164 The authors conjugated PEI-PEG-RGD and a sFlt-1 gene that encoded a soluble fragment of Flt-1 (VEGF receptor antagonist) and found that this non-viral gene delivery system enabled stable expression of sFlt-1 by endothelial cells. The expressed soluble Flt-1 fragment, coupled to exogenous VEGF, blocked Flt-1 receptor binding and inhibited cultured endothelial cell proliferation.164 Using another approach, Hosseinkhani and Tabata investigated the feasibility of tumor targeting using a non-viral gene carrier synthesized from a genetically engineered silk-like polymer containing repeated RGD sequences(Pronectin F + ).173 When cationized, Pronectin F + -plasmid DNA complexes with or without pegylation were intravenously injected into mice carrying a subcutaneous Meth-AR-1 fibrosarcoma mass, and the level of gene expression in the tumor was significantly higher for the PEG-DNA complex relative to non-pegylated complexes and free plasmid DNA.

Although anti-angiogenic gene therapy is still in its infancy, the studies beginning to appear in the literature suggest the prospects of development of new polymer-based gene delivery systems with improved transfection efficiency and reduced toxicity. It appears that many of the targeting and biodistribution lessons learned in studies of polymer-based drug delivery to sites of angiogenesis may be applied to enhance the success of polymer based gene delivery as well.

Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook


Post a comment