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

Ricardo J. B. Pinto, Nicole S. Lameirinhas, Gabriela Guedes, Gustavo H. Rodrigues da Silva, Párástu Oskoei, Stefan Spirk, Helena Oliveira, Iola F. Duarte, Carla Vilela, Carmen S. R. Freire

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number2057
Issue number8
Publication statusPublished - 12 Aug 2021


  • Cellular exometabolomics
  • Cellular uptake
  • Cellulose nanocrystals
  • Chitosan
  • Fluorescein isothiocyanate
  • Folate receptor-positive cancer cells
  • Folic acid
  • Nanosystems
  • Physical adsorption

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Materials Science(all)


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