title: Cytotoxicity of folic acid conjugated hollow silica nanoparticles toward Caco2 and 3T3 cells, with and without encapsulated DOX.
abstract: Hollow silica nanoparticles of two sizes with and without a folic acid targeting ligand were synthesized. Fickian diffusion of the antitumor drug doxorubicin hydrochloride (DOX) was demonstrated by the produced nanoparticles, achieving a cumulative release of 73% and 45% for 215 nm and 430 nm particles respectively over a period of 500 h. The hollow silica nanoparticles presented a time and dose dependent toxicity, selective to human epithelial colorectal adenocarcinoma (Caco2) cells, over mouse embryonic fibroblast (3T3) cells. At 24h Caco2 cell viability was reduced to 66% using pure hollow silica at a concentration of 50 μg mL(-1), while that of 3T3 cells remained at 94% under the same conditions. The selective cytotoxicity of hollow silica nanoparticles was further enhanced by conjugation of folic acid and incorporation of DOX: at 24h and an equivalent DOX concentration of 0.5 μg mL(-1), viable Caco2 cells were reduced to 45% while 3T3 cells were reduced to 83%. Interestingly the equivalent dose of free DOX was more toxic to 3T3 than to Caco2 cells, reducing the 3T3 viability to 72% and the Caco2 viability to 80%, which is likely due to the presence of the p-glycoprotein pumps in Caco2 cells. Folic acid conjugation served to enhance the viability of both cell lines in this work. Careful optimization of the folate content should further improve the cell specificity of the hollow silica nanoparticles, thus providing a viable targeting platform for cancer therapy.
authors.affiliation: Department of Chemical Engineering, Curtin University, Kent Street, Bentley, WA 6102, Australia.
authors.forename: Kunal
authors.initials: K
authors.lastname: Patel
authors.affiliation: School of Pharmacy, CHIRI-Biosciences, Curtin University, Kent Street, Bentley, WA 6102, Australia.
authors.forename: Behin
authors.initials: B
authors.lastname: Sundara Raj
authors.affiliation: School of Pharmacy, CHIRI-Biosciences, Curtin University, Kent Street, Bentley, WA 6102, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Chemical Engineering, Curtin University, Kent Street, Bentley, WA 6102, Australia. Electronic address: x.lou@curtin.edu.au.
authors.forename: Xia
authors.initials: X
authors.lastname: Lou
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D012822:Silicon Dioxide; D004317:Doxorubicin; D005492:Folic Acid
keywords: Cytotoxicity; Doxorubicin hydrochloride; Drug delivery; Hollow silica nanoparticles