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.

Nanoscale drug delivery vehicles have been harnessed extensively as carriers for cancer chemotherapeutics. However, traditional pharmaceutical approaches for nanoformulation have been a challenge with molecules that exhibit incompatible physicochemical properties, such as platinum-based chemotherapeutics. Here we propose a paradigm based on rational design of active molecules that facilitate supramolecular assembly in the nanoscale dimension. Using cisplatin as a template, we describe the synthesis of a unique platinum (II) tethered to a cholesterol backbone via a unique monocarboxylato and O→Pt coordination environment that facilitates nanoparticle assembly with a fixed ratio of phosphatidylcholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000]. The nanoparticles formed exhibit lower IC 50 values compared with carboplatin or cisplatin in vitro, and are active in cisplatin-resistant conditions. Additionally, the nanoparticles exhibit significantly enhanced in vivo antitumor efficacy in murine 4T1 breast cancer and in K-Ras LSL/+ /Pten fl/fl ovarian cancer models with decreased systemicand nephro-toxicity. Our results indicate that integrating rational drug design and supramolecular nanochemistry can emerge as a powerful strategy for drug development. Furthermore, given that platinum-based chemotherapeutics form the frontline therapy for a broad range of cancers, the increased efficacy and toxicity profile indicate the constructed nanostructure could translate into a nextgeneration platinum-based agent in the clinics.chemotherapy | nanomedicine

Surprisingly, despite its very high mobility in a single crystal, rubrene shows very low mobility in vacuum-sublimed or solution-processed organic thin-film transistors. We synthesized several rubrene analogues with electron-withdrawing and electron-donating substituents and found that most of the substituted rubrenes are not planar in the solid state. Moreover, we conclude (based on experimental and calculated data) that even parent rubrene is not planar in solution and in thin films. This discovery explains why high mobility is reported in rubrene single crystals, but rubrene shows very low field-effect mobility in thin films. The substituted rubrenes obtained in this work have significantly better solubility than parent rubrene and some even form films and not crystals after evaporation of the solvent. Thus, substituted rubrenes are promising materials for organic light-emitting diode (OLED) applications.