Functionalized nanoparticles potentiate the delivery of anticancer drugs to colorectal cancer cells

Functionalized nanoparticles have been explored for cancer treatment, as a mean to efficiently deliver the anti-cancer drugs to tumor-site, improving the outcome of those molecules. In this work, polymericpoly(lactic-co-glycolic)-polyethyleneglicol (PLGA-PEG) nanoparticles were produced and surface-functionalized with an antibody targeting the Carcinoembryonic Antigen (CEA) of intestinal epithelial cells. CEA is overexpressed in several cancers, including colorectal cancer. Nanoparticles were loaded with paclitaxel (PTX), an anticancer drug. Physicochemical properties, cytotoxicity and targeting ability of the nanoparticles against two intestine epithelial carcinoma cell lines, CEA-expressing Caco-2 clone and non-CEA-expressing SW480, were assessed. Results showed nanoparticles with a size of around 200 nm, effectively loaded with paclitaxel and functionalized. The particles proven to be non-cytotoxic against the intestine cell lines. The targeting ability of functionalized nanoparticles to Caco-2 CEA expressing cells was confirmed by flow cytometry, in opposite to SW480 cells. This specific interaction provide these particles ability to be used as targeted systems for colorectal cancer therapeutics.

Authors and Affiliations:

Inês Pereira (i3S, Porto; INEB, Porto; FEUP, Porto); Flávia Sousa (i3S, Porto; INEB, Porto; CESPU, Gandra; ICBAS, Porto); Patrick Kennedy (i3S, Porto; INEB, Porto; IPATIMUP, Porto; ICBAS, Porto) and Bruno Samento (i3S, Porto; INEB, Porto; CESPU, Gandra; School of Pharmacy, Queen’s University Belfast, Belfast).

Abstract:

Bioengineered functionalized nanoparticles have extensively been proposed in recent years to efficiently deliver anti-cancer drugs to the tumour site, by targeting the cancer cells and improving the therapeutic efficiency of active molecules. In this work, polymeric poly (lactic-co- glycolic)-polyethyleneglycol (PLGA-PEG) nanoparticles were produced by nanoprecipitation and loaded with paclitaxel, following surface-functionalized with a monoclonal antibody targeting the carcinoembryonic antigen (CEA) of intestinal epithelial cells. Physicochemical properties, cytotoxicity and targeting ability of the nanoparticles against two intestine epithelial carcinoma cell lines, CEA-expressing Caco-2 clone and non-CEA-expressing SW480, were assessed. Results showed successful production of nanoparticles around 200 nm, and close to charge neutrality, encapsulating up to 99% of paclitaxel. Functionalized nanoparticles were further constructed, demonstrating to be non-cytotoxic against intestinal cells. The targeting ability of functionalized nanoparticles to Caco-2 CEA expressing cells was confirmed by flow cytometry, in opposite to SW480 cells. Overall, the surface-modified PLGA-PEG nanoparticles with the CEA-targeting antibody were successfully developed as nanocarriers for paclitaxel and interacted with CEA expressing cells. This specific interaction provide these particles ability to be used as targeted systems for colorectal cancer therapeutics.

Journal: International Journal of Pharmaceutics

Link: https://doi.org/10.1016/j.ijpharm.2018.08.016