title: PEGylated nanographene oxide for delivery of water-insoluble cancer drugs.
abstract: It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nanographene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO-PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analogue, SN38, noncovalently via pi-pi stacking. The resulting NGO-PEG-SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO-PEG-SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Robinson
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.forename: Hongjie
authors.initials: H
authors.lastname: Dai
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000077146:Irinotecan; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry; D010087:Oxides / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013499:Surface Properties; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010087:Oxides; D014867:Water; D011092:Polyethylene Glycols; D002244:Carbon; D000077146:Irinotecan; D002166:Camptothecin