title: Fullerenol-cytotoxic conjugates for cancer chemotherapy.
abstract: In the present study, we report the novel application of polyhydroxylated fullerenes (fullerenols) in cancer drug delivery. The facile synthetic procedure for generating multiple hydroxyl groups on the fullerene cage offers scope for high drug loading in addition to conferring hydrophilicity. Doxorubicin, a first line cancer chemotherapeutic, was conjugated to fullerenols through a carbamate linker, achieving ultrahigh loading efficiency. The drug-fullerenol conjugate was found to be relatively stable in phosphate buffer saline but temporally released the active drug when incubated with tumor cell lysate. The fullerenol-doxorubicin conjugate suppressed the proliferation of cancer cell-lines in vitro through a G2-M cell cycle block, resulting in apoptosis. Furthermore, in an in vivo murine tumor model, fullerenol-doxorubicin exhibited comparable antitumor efficacy as free drug without the systemic toxicity of free doxorubicin. Additionally, we demonstrate that the fullerenol platform can be extended to other chemotherapeutic agents, such as the slightly water-soluble cisplatin, and can emerge as a new paradigm in the management of cancer.
authors.affiliation: Laboratory of Nanomedicine, HST Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, USA.
authors.forename: Padmaparna
authors.initials: P
authors.lastname: Chaudhuri
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Paraskar
authors.forename: Shivani
authors.initials: S
authors.lastname: Soni
authors.forename: Raghunath A
authors.initials: RA
authors.lastname: Mashelkar
authors.forename: Shiladitya
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D005434:Flow Cytometry; D037741:Fullerenes / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides / Q000737:chemistry; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D037741:Fullerenes; D006878:Hydroxides; D014867:Water; C108127:fullerenol; D004317:Doxorubicin; C031356:hydroxide ion; D002945:Cisplatin