PEGylated nanographene oxide for delivery of water-insoluble cancer drugs.
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.
Liu
Zhuang
Z
Department of Chemistry, Stanford University, Stanford, California 94305, USA.
Robinson
Joshua T
JT
Sun
Xiaoming
X
Dai
Hongjie
H
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*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D010087:Oxides; D014867:Water; D011092:Polyethylene Glycols; D002244:Carbon; D000077146:Irinotecan; D002166:Camptothecin