Limited penetration of
antineoplastic agents is one of the contributing factors for
chemotherapy failure of many solid
tumors. In order to enhance
drug penetration into solid
cancer, especially, into the avascular regions inside
tumors, we proposed
cyclic RGD peptide functionalized PEGylated
poly(trimethylene carbonate) nanoparticles (c(RGDyK)-NP). By
integrin-mediated transcytosis and enhanced
drug permeation, c(RGDyK)-NP could access the neoplastic cells distant from blood vessels, and consequently, avoiding the capability of
cancer regeneration from these
tumor cells. In the present study, the solid
tumor penetration, homing specificity and anticancer efficacy were evaluated both on the ex vivo 3D
tumor spheroids and on the subcutaneous xenograft mice model. In comparison with conventional nanoparticles (NP/PTX) and
Taxol, c(RGDyK)-NP/PTX showed the strongest penetration and accumulation into 3D
tumor spheroids, a marked
tumor-homing specificity in vivo and the greatest
tumor growth inhibitory effect in vitro and in vivo. Histochemistry analysis revealed that no obvious histopathological abnormalities or lesions were observed in major organs after
intravenous administration with the treatment doses. In conclusion,
cyclic RGD peptide-conjugated PEG-PTMC nanoparticle could facilitate
drug penetration and accumulation in
tumor tissues and may be a promising vehicle for enhancing the
chemotherapy of solid
cancers.