Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin.
The platinum-based anticancer drugs cisplatin, carboplatin, and oxaliplatin are an important component of chemotherapy but are limited by severe dose-limiting side effects and the ability of tumors to develop resistance rapidly. These drugs can be improved through the use of drug-delivery vehicles that are able to target cancers passively or actively. In this study, we have tethered the active component of the anticancer drug oxaliplatin to a gold nanoparticle for improved drug delivery. Naked gold nanoparticles were functionalized with a thiolated poly(ethylene glycol) (PEG) monolayer capped with a carboxylate group. [Pt(1R,2R-diaminocyclohexane)(H(2)O)(2)]2NO(3) was added to the PEG surface to yield a supramolecular complex with 280 (+/-20) drug molecules per nanoparticle. The platinum-tethered nanoparticles were examined for cytotoxicity, drug uptake, and localization in the A549 lung epithelial cancer cell line and the colon cancer cell lines HCT116, HCT15, HT29, and RKO. The platinum-tethered nanoparticles demonstrated as good as, or significantly better, cytotoxicity than oxaliplatin alone in all of the cell lines and an unusual ability to penetrate the nucleus in the lung cancer cells.
Centre for Molecular Nanometrology, Department of Pure and Applied Chemistry, Thomas Graham Building, University of Strathclyde, 295 Cathedral Street, G1 1XL Glasgow, United Kingdom.
Sarah D
SD
Brown
Paola
P
Nativo
Jo-Ann
JA
Smith
David
D
Stirling
Paul R
PR
Edwards
Balaji
B
Venugopal
David J
DJ
Flint
Jane A
JA
Plumb
Duncan
D
Graham
Nial J
NJ
Wheate
D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity; D000077150:Oxaliplatin; D011092:Polyethylene Glycols / Q000737:chemistry; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004337:Drug Carriers; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011092:Polyethylene Glycols; D006046:Gold