Cellulose Nanocrystals/Chitosan-Based Nanosystems: Synthesis, Characterization, and Cellular Uptake on Breast Cancer Cells


Cellulose nanocrystals (CNCs) are elongated biobased nanostructures with unique characteristics that can be explored as nanosystems in cancer treatment. Herein, the synthesis, characterization, and cellular uptake on folate receptor (FR)-positive breast cancer cells of nanosystems based on CNCs and a chitosan (CS) derivative are investigated. The physical adsorption of the CS derivative, containing a targeting ligand (folic acid, FA) and an imaging agent (fluorescein isothiocyanate, FITC), on the surface of the CNCs was studied as an eco-friendly methodology to functionalize CNCs. The fluorescent CNCs/FA-CS-FITC nanosystems with a rod-like morphology showed good stability in simulated physiological and non-physiological conditions and non-cytotoxicity towards MDA-MB-231 breast cancer cells. These functionalized CNCs presented a concentration-dependent cellular internalization with a 5-fold increase in the fluorescence intensity for the nanosystem with the higher FA content. Furthermore, the exometabolic profile of the MDA-MB-231 cells exposed to the CNCs/FA-CS-FITC nanosystems disclosed a moderate impact on the cells' metabolic activity, limited to decreased choline uptake and increased acetate release, which implies an anti-proliferative effect. The overall results demonstrate that the CNCs/FA-CS-FITC nanosystems, prepared by an eco-friendly approach, have a high affinity towards FR-positive cancer cells and thus might be applied as nanocarriers with imaging properties for active targeted therapy.



subject category

Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied


Pinto, RJB; Lameirinhas, NS; Guedes, G; da Silva, GRH; Oskoei, P; Spirk, S; Oliveira, H; Duarte, IF; Vilela, C; Freire, CSR

our authors


This work was developed within the scope of the projects CICECO-Aveiro Institute of Materials (UIDB/50011/2020 & UIDP/50011/2020) and CESAM-Centre for Environmental and Marine Studies (UIDB/50017/2020 & UIDP/50017/2020) financed by national funds through the Portuguese Foundation for Science and Technology (FCT)/MCTES. The research contract of R.J.B.P. was funded by national funds (OE), through FCT in the scope of the framework contract foreseen in the numbers 4, 5, and 6 of the article 23, of the Decree-Law 57/2016, of 29 August, changed by Law 57/2017, of 19 July. FCT is also acknowledged for the doctoral grant to N.S.L. (SFRH/BD/140229/2018) and the research contracts under Scientific Employment Stimulus to H.O. (CEECIND/04050/2017), C.V. (CEECIND/00263/2018) and C.S.R.F. (CEECIND/00464/2017). FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) and the University of Aveiro are acknowledged for the doctoral grants to G.H.R.d.S. (2018/24814-0) and P.O. (BD/REIT/8623/2020), respectively. The NMR spectrometer is part of the National NMR Network (PTNMR), partially supported by Infrastructure Project N degrees 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).

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