So far, the success of anticancer nanomedicines has been moderate due to their lack of adequate targeting properties and/or to their difficulties for penetrating tumors. Here we report a multifunctional drug nanocarrier consisting of hyaluronic acid nanocapsules conjugated with the tumor homing peptide tLyp1, which exhibits both, dual targeting properties (to the tumor and to the lymphatics), and enhanced tumor penetration. Data from a 3D co-culture in vitro model showed the capacity of these nanocapsules to interact with the NRP1 receptors over-expressed in cancer cells. The targeting capacity of the nanocapsules was evidenced in orthotopic lung cancer-bearing mice, using docetaxel as a standard drug. The results showed a dramatic accumulation of docetaxel in the tumor (37-fold the one achieved with Taxotere®). This biodistribution profile correlated with the high efficacy shown in terms of tumor growth regression and drastic reduction of metastasis in the lymphatics. When efficacy was validated in a pancreatic patient-derived tumor, the nanocapsule's activity was comparable to that of a dose ten times higher of Abraxane®. Multi-functionality was found to be the key to the success of this new therapy.
Keywords: Anti-cancer drug delivery; Lymphatic targeting; Metastasis; Nanocapsules; Tumor homing peptide; Tumor targeting.
Copyright © 2018. Published by Elsevier B.V.