title: Covalently combining carbon nanotubes with anticancer agent: preparation and antitumor activity.
abstract: A multiwalled carbon nanotube (MWNT)-based drug delivery system was developed by covalently combining carbon nanotubes with the antitumor agent 10-hydroxycamptothecin (HCPT) using hydrophilic diaminotriethylene glycol as the spacer between nanotube and drug moieties. The surface functionalizations of the nanotube were carried out by enrichment of carboxylic groups with optimized oxidization treatment, followed by covalently linking hydrophilic diaminotriethylene glycol via amidation reaction, and then HCPT was chemically attached to carbon nanotubes through a cleavable ester linkage. It is demonstrated that the obtained MWNT-HCPT conjugates are superior in antitumor activity both in vitro and in vivo to clinical HCPT formulation. In vivo single photon emission computed tomography (SPECT) imaging and ex vivo gamma scintillation counting analyses reveal that MWNT-HCPT conjugates have relatively long blood circulation and high drug accumulation in the tumor site. These properties together with the enhanced cell uptake and multivalent presentation of HCPT on a single nanotube benefit substantially the antitumor effects and would boost significantly the applications of carbon nanotubes in the biomedicine field.
authors.affiliation: Laboratory of Mesoscopic Chemistry and Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Rutian
authors.initials: R
authors.lastname: Li
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Bian
authors.forename: Zhenshu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Dan
authors.initials: D
authors.lastname: Ding
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Jia
authors.forename: Xiqun
authors.initials: X
authors.lastname: Jiang
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001692:Biological Transport; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D002417:Cattle; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D019855:Ethylene Glycol / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry*; D012995:Solubility; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D059004:Topoisomerase I Inhibitors; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004952:Esters; D037742:Nanotubes, Carbon; D059004:Topoisomerase I Inhibitors; D014867:Water; C028098:10-hydroxycamptothecin; D019855:Ethylene Glycol; D002166:Camptothecin