Fucoidan/chitosan nanoparticles functionalized with anti-ErbB-2 target breast cancer cells and impair tumor growth in vivo

The work herein presented reports the development of fucoidan/chitosan nanoparticles (NPs) loaded with gemcitabine and functionalized with ErbB-2 antibody at their surface (NPs + Gem + Ab). The maximum immobilization of ErbB-2 on NPs' surface was set at 10 mu g mL(-1) and resulted in NPs with a size around 160 nm, a polydispersity index of 0.18, and a zeta potential of 21 mV. ErbB-2 is overexpressed in some subtypes of breast cancers, and the targeting capability of the NPs + Gem + Ab system was confirmed by an increased cellular uptake of SKBR3 cells (ErbB-2 positive) when compared to MDA-MB-231 (ErbB-2 negative). To validate the targeting efficacy of NPs + Gem + Ab, a co-culture system with human endothelial and SKBR3 cells was established. Cytotoxic effects over endothelial cells were similar for all the tested conditions (between 25 and 30%). However, the NPs + Gem + Ab system presented increased toxicity over breast cancer cells, above 80% after 24 h, when compared to free Gem and NPs + Gem (around 15% and 20%, respectively). In vivo studies demonstrated that the developed targeting system significantly reduced tumor growth and the appearance of lung metastasis compared to untreated controls. In summary, the efficacy of the NPs + Gem + Ab system to target cancer cells was established and validated both in vitro and in vivo, being a compelling alternative strategy to current chemotherapeutic approaches.

This work was developed under the scope of the Structured projects for R&D&I NORTE-01-0145-FEDER-000013/21/23 supported by the Northern Portugal Regional Operational Programme Norte 2020, under the Portugal 2020 Partnership Agreement. The authors would like also to thank Norte 2020 for financing the PhD scholarship of C.O. "Norte-085369-000037" and the Portuguese Foundation for Science and Technology for the Investigator grant of A.M. (IF/00376/2014). The authors would also like to acknowledge Teresa Oliveira for her insights regarding the histological analysis performed for the in vivo studies.