Folic Acid-Conjugated Cellulose Nanocrystals Show High Folate-Receptor Binding Affinity and Uptake by KB and Breast Cancer Cells | Zendy

Katelyn Rose Bittleman | Zendy; Shuping Dong | Zendy; Maren Roman | Zendy; Yong Woo Lee | Zendy

Open Access

Folic Acid-Conjugated Cellulose Nanocrystals Show High Folate-Receptor Binding Affinity and Uptake by KB and Breast Cancer Cells

Author(s) -

Katelyn Rose Bittleman,

Shuping Dong,

Maren Roman,

Yong Woo Lee

Publication year - 2018

Publication title -

acs omega

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.779

H-Index - 40

ISSN - 2470-1343

DOI - 10.1021/acsomega.8b01619

Subject(s) - endocytosis , internalization , nanocarriers , folate receptor , chemistry , conjugated system , confocal microscopy , fluorescein isothiocyanate , cancer cell , receptor mediated endocytosis , biophysics , biochemistry , drug delivery , cell , microbiology and biotechnology , biology , cancer , fluorescence , genetics , physics , organic chemistry , quantum mechanics , polymer

The study evaluates cellulose nanocrystals (CNCs) as nanocarriers for targeted, intracellular delivery of molecular agents. CNCs were labeled with fluorescein-5'-isothiocyanate as an imaging agent and conjugated to folic acid (FA) as a targeting ligand. The CNC conjugates were characterized by UV-vis spectroscopy, ζ-potential analysis, dynamic light scattering, and atomic force microscopy. Cellular binding/uptake of the FA-conjugated CNCs by KB and MDA-MB-468 cells was quantified with cellular uptake assays. Internalization of the particles was confirmed by confocal microscopy. Uptake mechanisms were determined by inhibition studies with chlorpromazine and genistein. Binding affinity was qualitatively assessed with a free folate inhibition assay. Both KB and MDA-MB-468 cells exhibited significant and folate-receptor specific binding/uptake of FA-conjugated CNCs. Clathrin-mediated endocytosis was a significant uptake mechanism in both cell types, whereas caveolae-mediated endocytosis only played a significant role in MDA-MB-468 cells. Uptake inhibition of FA-conjugated CNCs by KB cells required high concentrations (>1 mM) of free FA. The observed FR-specific internalization of FA-conjugated CNCs by FR-positive cancer cells and tumors and their remarkable high affinity for the FR demonstrate the great potential of CNCs as novel nanocarriers for imaging agents and chemotherapeutics in the early detection and treatment of cancer.

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