title: Designing Theranostic Agents Based on Pluronic Stabilized Gold Nanoaggregates Loaded with Methylene Blue for Multimodal Cell Imaging and Enhanced Photodynamic Therapy.
abstract: At present, multifunctional noble metal-based nanocomposites are extensively investigated for their potential in performing cellular imaging, diagnostics, and therapy by integration of unique plasmonic properties with the spectroscopic expression and therapeutic activity of appropriate drug. In this work, we report the fabrication of 3-dimensional (3-D) close-packed nanoassemblies of gold nanoparticles by controlling the aggregation of individual nanoparticles in solution and subsequent stabilization of formed aggregates by Pluronic block copolymer (F127) coating. Besides conferring high stability, Pluronic mediates the loading of Methylene Blue (MB) molecules which exhibit interesting spectroscopic and photochemical properties to be employed as both optical label and photosensitizing drug. Indeed, here we demonstrate the pertinence of the fabricated nanoassemblies to provide optical imaging of murine colon carcinoma cells (C-26) via both Raman and fluorescence signals collected from MB molecules, specifically by using scanning confocal surface-enhanced resonant raman spectroscopy (SERRS) and fluorescence lifetime imaging microscopy (FLIM) techniques. The specific configuration of as fabricated nanoassemblies allows a small population of MB molecules to be located in very small areas between the aggregated nanoparticles ("hot spots") to provide SERRS signal while the other population remains captured in Pluronic coating and preserves both its fluorescence signal and singlet-oxygen generation capability. Remarkably, we demonstrate an enhanced photodynamic therapeutic activity of MB-loaded gold nanoaggregates against murine colon carcinoma cells (C-26), as compared to the free photosensitizer. To our knowledge, this is the first report on plasmonic nanoplatforms conveying photosensitizing drug into cells to operate as optical label via both SER(R)S and FLIM and to perform enhanced photodynamic therapy.
authors.affiliation: †Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Physics, and ‡Molecular Biology Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Biology, Babes-Bolyai University, M. Kogalniceanu Str 1, 400084 Cluj-Napoca, Romania.
authors.forename: Timea
authors.initials: T
authors.lastname: Simon
authors.affiliation: †Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Physics, and ‡Molecular Biology Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Biology, Babes-Bolyai University, M. Kogalniceanu Str 1, 400084 Cluj-Napoca, Romania.
authors.forename: Monica
authors.initials: M
authors.lastname: Potara
authors.affiliation: †Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Physics, and ‡Molecular Biology Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Biology, Babes-Bolyai University, M. Kogalniceanu Str 1, 400084 Cluj-Napoca, Romania.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Gabudean
authors.affiliation: †Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Physics, and ‡Molecular Biology Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Biology, Babes-Bolyai University, M. Kogalniceanu Str 1, 400084 Cluj-Napoca, Romania.
authors.forename: Emilia
authors.initials: E
authors.lastname: Licarete
authors.affiliation: †Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Physics, and ‡Molecular Biology Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Biology, Babes-Bolyai University, M. Kogalniceanu Str 1, 400084 Cluj-Napoca, Romania.
authors.forename: Manuela
authors.initials: M
authors.lastname: Banciu
authors.affiliation: †Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Physics, and ‡Molecular Biology Center, Interdisciplinary Research Institute in Bio-Nano-Sciences and Faculty of Biology, Babes-Bolyai University, M. Kogalniceanu Str 1, 400084 Cluj-Napoca, Romania.
authors.forename: Simion
authors.initials: S
authors.lastname: Astilean
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D058948:Cell Tracking / Q000379:methods*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003287:Contrast Media / Q000138:chemical synthesis; D006046:Gold / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D008751:Methylene Blue / Q000737:chemistry; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D058726:Nanoconjugates / Q000737:chemistry / Q000627:therapeutic use / Q000648:ultrastructure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011095:Polyethylenes / Q000737:chemistry; D011126:Polypropylenes / Q000737:chemistry; D000068936:Theranostic Nanomedicine / Q000379:methods; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D053769:Nanocapsules; D058726:Nanoconjugates; D017319:Photosensitizing Agents; D011095:Polyethylenes; D011126:Polypropylenes; D006046:Gold; C078661:UCON 50-HB-5100; D008751:Methylene Blue
keywords: FLIM; PDT; SERS; gold; methylene blue; nanoaggregates