title: Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy.
abstract: We report a novel cancer-targeted nanomedicine platform for imaging and prospect for future treatment of unresected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, novel low-oxygen graphene nanosheets were chemically modified with polypropylenimine dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular design prevents fluorescence quenching of the Pc by graphene nanosheets, providing the possibility of fluorescence imaging. Furthermore, the developed nanoplatform was conjugated with poly(ethylene glycol), to improve biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide, for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation of single wavelength was used for both heat generation by the graphene nanosheets (photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%-95% at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to the synergistic effects of generated ROS and mild hyperthermia. An animal study confirmed that Pc loaded into the nanoplatform can be employed as a NIR fluorescence agent for imaging-guided drug delivery. Hence, the newly developed Pc-graphene nanoplatform has the significant potential as an effective NIR theranostic probe for imaging and combinatorial phototherapy.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Olena
authors.initials: O
authors.lastname: Taratula
authors.affiliation: Department of Chemistry, Rutgers University-Newark, Newark, NJ, USA.
authors.forename: Mehulkumar
authors.initials: M
authors.lastname: Patel
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Canan
authors.initials: C
authors.lastname: Schumann
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Naleway
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Addison J
authors.initials: AJ
authors.lastname: Pang
authors.affiliation: Department of Chemistry, Rutgers University-Newark, Newark, NJ, USA.
authors.forename: Huixin
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Oleh
authors.initials: O
authors.lastname: Taratula
mesh_terms: D045744:Cell Line, Tumor; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D054833:Isoindoles; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology; D010789:Phototherapy / Q000379:methods*
chemical_list: D007211:Indoles; D054833:Isoindoles; D006108:Graphite; C013647:phthalocyanine
keywords: graphene nanosheets; photodynamic therapy; photothermal therapy; phthalocyanine; theranostic
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