title: Covalent linkage of nanodiamond-paclitaxel for drug delivery and cancer therapy.
abstract: A nanoparticle-conjugated cancer drug provides a novel strategy for cancer therapy. In this study, we manipulated nanodiamond (ND), a carbon nanomaterial, to covalently link paclitaxel for cancer drug delivery and therapy. Paclitaxel was bound to the surface of 3-5 nm sized ND through a succession of chemical modifications. The ND-paclitaxel conjugation was measured by atomic force microscope and nuclear magnetic resonance spectroscopy, and confirmed with infrared spectroscopy by the detection of deuterated paclitaxel. Treatment with 0.1-50 microg ml(-1) ND-paclitaxel for 48 h significantly reduced the cell viability in the A549 human lung carcinoma cells. ND-paclitaxel induced both mitotic arrest and apoptosis in A549 cells. However, ND alone or denatured ND-paclitaxel (after treatment with strong alkaline solution, 1 M NaOH) did not induce the damage effects on A549 cells. ND-paclitaxel was taken into lung cancer cells in a concentration-dependent manner using flow cytometer analysis. The ND-paclitaxel particles were located in the microtubules and cytoplasm of A549 cells observed by confocal microscopy. Furthermore, ND-paclitaxel markedly blocked the tumor growth and formation of lung cancer cells in xenograft SCID mice. Together, we provide a functional covalent conjugation of ND-paclitaxel, which can be delivered into lung carcinoma cells and preserves the anticancer activities on the induction of mitotic blockage, apoptosis and anti-tumorigenesis.
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Kuang-Kai
authors.initials: KK
authors.lastname: Liu
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Zheng
authors.forename: Chi-Ching
authors.initials: CC
authors.lastname: Wang
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Chiu
authors.forename: Chia-Liang
authors.initials: CL
authors.lastname: Cheng
authors.forename: Yu-Shiu
authors.initials: YS
authors.lastname: Lo
authors.forename: Chinpiao
authors.initials: C
authors.lastname: Chen
authors.forename: Jui-I
authors.initials: JI
authors.lastname: Chao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002244:Carbon / Q000737:chemistry*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002244:Carbon; D017239:Paclitaxel