Paclitaxel-trastuzumab mixed nanovehicle to target HER2-overexpressing tumors

© 2019 by the authors.Paclitaxel is one of the most widely used chemotherapeutic agents thanks to its effectiveness and broad spectrum of antitumor activity. However, it has a very poor aqueous solubility and a limited specificity. To solve these handicaps, a novel paclitaxel-trastuzumab targeted transport nanosystem has been developed and characterized in this work to specifically treat cancer cells that overexpress the human epidermal growth factor receptor-2 (HER2). Methods: Alginate and piperazine nanoparticles were synthetized and conjugated with paclitaxel:β-cyclodextrins complexes and trastuzumab. Conjugated nanoparticles (300 nm) were characterized and their internalization in HER2-overexpressing tumor cells was analyzed by immunofluorescence. Its specific antitumor activity was studied in vitro using human cell lines with different levels of HER2-expression. Results: In comparison with free paclitaxel:β-cyclodextrins complexes, the developed conjugated nanovehicle presented specificity for the treatment of HER2-overpressing cells, in which it was internalized by endocytosis. Conclusions: It seems that potentially avoiding the conventional adverse effects of paclitaxel treatment could be possible with the use of the proposed mixed nanovehicle, which improves its bioavailability and targets HER2-positive cancer cells.This work was supported by a UE ERC Starting Grant (MYCAP. Development of a technology to produce microcapsules, based on the formation of drops from viscous non-Newtonians liquids sprayed through fan-jet nozzles, to use in cancer therapy), by the Spanish Ministry of Economy and Competitiveness (BFU2012-39151, BFU2015-71371R, CTQ2016-78988-R, PI15/00684, and FEDER), the CRIS Cancer Foundation and the Scientific Foundation of the Spanish Association Against Cancer (AECC). CN is recipient of a predoctoral contract from the Junta de Castilla y León, co-funded by the European Social Foundation (EDU/602/2016) and AC was supported by a doctoral fellowship from Coordination for the Improvement of Higher Education Personnel (CAPES) from the Ministry of Education of Brazil