Antiangiogenic
peptide drugs have received much attention in the fields of
tumor therapy and
tumor imaging because they show promise in the targeting of
integrins such as alpha(v)beta(3) on angiogenic endothelial cells. However, systemic antiangiogenic
peptide drugs have short half-lives in vivo, resulting in fast serum clearance via the kidney, and thus the
therapeutic effects of such drugs remain modest. In this study, we prepared self-assembled
glycol chitosan nanoparticles and explored whether this construct might function as a prolonged and sustained drug delivery system for
RGD peptide, used as an antiangiogenic model
drug in
cancer therapy.
Glycol chitosan hydrophobically modified with 5beta-cholanic
acid (HGC) formed nanoparticles with a diameter of 230 nm, and
RGD peptide was easily encapsulated into HGC nanoparticles (yielding RGD-HGC nanoparticles) with a high loading efficiency (>85%). In vitro work demonstrated that RGD-HGC showed prolonged and sustained release of RGD, lasting for 1 week. RGD-HGC also inhibited HUVEC adhesion to a
beta ig-h3 protein-coated surface, indicating an antiangiogenic effect of the
RGD peptide in the HGC nanoparticles. In an in vivo study, the antiangiogenic
peptide drug formulation of RGD-HGC markedly inhibited bFGF-induced angiogenesis and decreased
hemoglobin content in
Matrigel plugs. Intratumoral administration of RGD-HGC significantly decreased
tumor growth and microvessel density compared to native
RGD peptide injected either intravenously or intratumorally, because the RGD-HGC formulation strongly enhanced the antiangiogenic and antitumoral efficacy of
RGD peptide by affording prolonged and sustained
RGD peptide delivery locally and regionally in solid
tumors.