Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting.
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.
Macromolecules and Interfaces Institute, ‡School of Biomedical Engineering and Sciences, §Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, and ∥Department of Sustainable Biomaterials, Virginia Tech , Blacksburg, Virginia 24061, United States.
Shuping
S
Dong
Hyung Joon
HJ
Cho
Yong Woo
YW
Lee
Maren
M
Roman
D000818:Animals; D021941:Caveolae / Q000378:metabolism; D002482:Cellulose / Q000737:chemistry*; D002746:Chlorpromazine / Q000494:pharmacology; D002966:Clathrin / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D058973:Folate Receptors, GPI-Anchored / Q000032:analysis / Q000378:metabolism*; D005492:Folic Acid / Q000737:chemistry*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
D002966:Clathrin; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D002482:Cellulose; D005492:Folic Acid; D019833:Genistein; D002746:Chlorpromazine