Synthesis and Cellular Uptake of Folic Acid-Conjugated Cellulose Nanocrystals for Cancer Targeting

Abstract

Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis.

Polyrhodanine Coated Cellulose Nanocrystals: A Sustainable Antimicrobial Agent

“…CNC@PR still displayed peaks similar to the typical reflection planes of cellulose I, which is labeled in the diffraction pattern of pristine CNC, indicating that the chemical modification did not significantly alter the crystal lattice. However, the degree of crystallinity of the particles decreased, which can be attributed to the coating of amorphous polyrhodanine on the surface (The degree of crystallinity was determined to be 0.93, 0.65 and 0.58 for CNC, CNC@PR 5 and CNC@PR 8, respectively using the Buschle-Diller and Zeronian Equation 54,55 , see supporting information).…”

Folate Conjugated Cellulose Nanocrystals Potentiate Irreversible Electroporation-induced Cytotoxicity for the Selective Treatment of Cancer Cells

“…Hydroxyl groups on the CNC surface were partially converted to carboxyl groups (CNC-COOH). Determined by atomic force microscopy CNCs are rod-like nanoparticles with a width of 4-5 nm and a length of 100-150 nm (30). More detailed information on the preparation and characterization of nanoparticles can be found in Dong et al (18).…”

Toxicity of Cellulose Nanocrystals: A Review

“…Consequently, cellulosic nanomaterials are being studied for a number of potential applications, including polymer nanocomposites, transparent or chiral films, rheology modifiers and hydrogels, drug-delivery vehicles, artificial blood vessels, and wound dressings. [1][2][3][4][5][6][7] However, before a material or technology can be commercialized, its impact on the environment and human health needs to be thoroughly assessed. The literature on cellulosic nanomaterial toxicity has recently been summarized in two review articles covering the use of cellulosic nanomaterials in biomedicine.…”