Abstract
The low tumor permeability of nanomedicines is a major challenge for their application in tumor therapy. Reducing the size of nanomedicines or integrating penetrating peptides has been demonstrated to be very helpful to improve the tumor permeability of nanomedicines. In this paper, poly(amidoamine) (PAMAM) functionalized with the penetrating peptide CRGDK was designed as a drug carrier with a diameter of ∼5 nm. Paclitaxel (PTX) was used as a model drug and covalently linked to the carrier via a biocleavable ester bond. The CRGDK-functionalized drug-loaded nanoparticle exhibited a higher cellular uptake and a higher tumor accumulation and penetration than its nontargeted counterpart, which also endowed the functionalized nanomedicine with a higher antitumor efficiency than its nontargeted counterpart and the clinical Taxol formulation. The good performance of the peptide-bearing PAMAM-based nanomedicine indicates that our strategy is feasible to improve the tumor accumulation and penetration of nanomedicines.
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