title: Plasmonic nanocarrier grid-enhanced Raman sensor for studies of anticancer drug delivery.
abstract: Targeted drug delivery systems using nanoparticle nanocarriers offer remarkable promise for cancer therapy by discriminating against devastating cytotoxicity of chemotherapeutic drugs to healthy cells. To aid in the development of new drug nanocarriers, we propose a novel plasmonic nanocarrier grid-enhanced Raman sensor which can be applied for studies and testing of drug loading onto the nanocarriers, attachment of targeting ligands, dynamics of drug release, assessment of nanocarrier stability in biological environment, and general capabilities of the nanocarrier. The plasmonic nanogrid sensor offers strong Raman enhancement due to the overlapping plasmonic fields emanating from the nearest-neighbor gold nanoparticle nanocarriers and creating the enhancement "hot spots". The sensor has been tested for immobilization of an anticancer drug gemcitabine (2',2'-difluoro-2'-deoxycytidine, GEM) which is used in treatment of pancreatic tumors. The drawbacks of currently applied treatment include high systemic toxicity, rapid drug decay, and low efficacy (ca. 20%). Therefore, the development of a targeted GEM delivery system is highly desired. We have demonstrated that the proposed nanocarrier SERS sensor can be utilized to investigate attachment of targeting ligands to nanocarriers (attachment of folic acid ligand recognized by folate receptors of cancer cells is described). Further testing of the nanocarrier SERS sensor involved drug release induced by lowering pH and increasing GSH levels, both occurring in cancer cells. The proposed sensor can be utilized for a variety of drugs and targeting ligands, including those which are Raman inactive, since the linkers can act as the Raman markers, as illustrated with mercaptobenzoic acid and para-aminothiophenol.
authors.affiliation: Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kurzątkowska
authors.affiliation: Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA.
authors.forename: Ty
authors.initials: T
authors.lastname: Santiago
authors.affiliation: Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA. Electronic address: hepelmr@potsdam.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Hepel
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D015374:Biosensing Techniques / Q000295:instrumentation; D003692:Delayed-Action Preparations / Q000737:chemistry; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004867:Equipment Design; D005492:Folic Acid / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D013059:Spectrum Analysis, Raman / Q000295:instrumentation*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D003841:Deoxycytidine; D006046:Gold; D005492:Folic Acid; D005978:Glutathione; D000093542:Gemcitabine
keywords: AuNP nanocarriers; Gemcitabine drug release; Plasmonic nanogrid sensor; SERS