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Ultra-small glycan-passivated gold nanoparticles of <2nm diameter were funtionalised with a short HS-EG(8)-COOH ligand. The nanoparticles were subsequently labelled, in a stoichiometrically controllable manner, with integrin-binding peptide SIKVAV and the maytansinoid cytotoxin DM4. In vitro assays showed significantly increased integrin-mediated uptake of SIKVAV labelled nanoparticles in HepG2 cells. SIKVAV targeted nanoparticle binding was shown to be outcompeted with free SIKVAV peptide, indicating target specific uptake. DM4 was passively attached to nanoparticles via sulfhydryl ligand exchange at the gold nanoparticle surface, which rendered them highly cytotoxic (IC50 ~1 × 10−9M). In a rat model, pharmacokinetic studies showed that nanoparticle biodistribution was strongly altered by labelling with either peptide and DM4 moieties.

SIKVAV peptide functionalized ultra-small gold nanoparticles for selective targeting of α6β1 integrin in hepatocellular carcinoma