title: Two-photon fluorescence imaging and bimodal phototherapy of epidermal cancer cells with biocompatible self-assembled polymer nanoparticles.
abstract: We have developed herein an engineered polymer-based nanoplatform showing the convergence of two-photon fluorescence imaging and bimodal phototherapeutic activity in a single nanostructure. It was achieved through the appropriate choice of three different components: a β-cyclodextrin-based polymer acting as a suitable carrier, a zinc phthalocyanine emitting red fluorescence simultaneously as being a singlet oxygen ((1)O2) photosensitizer, and a tailored nitroaniline derivative, functioning as a nitric oxide (NO) photodonor. The self-assembly of these components results in photoactivable nanoparticles, approximately 35 nm in diameter, coencapsulating a multifunctional cargo, which can be delivered to carcinoma cells. The combination of steady-state and time-resolved spectroscopic and photochemical techniques shows that the two photoresponsive guests do not interfere with each other while being enclosed in their supramolecular container and can thus be operated in parallel under control of light stimuli. Specifically, two-photon fluorescence microscopy allows mapping of the nanoassembly, here applied to epidermal cancer cells. By detecting the red emission from the phthalocyanine fluorophore it was also possible to investigate the tissue distribution after topical delivery onto human skin ex vivo. Irradiation of the nanoassembly with visible light triggers the simultaneous delivery of cytotoxic (1)O2 and NO, resulting in an amplified cell photomortality due to a combinatory effect of the two cytotoxic agents. The potential of dual therapeutic photodynamic action and two-photon fluorescence imaging capability in a single nanostructure make this system an appealing candidate for further studies in biomedical research.
authors.affiliation: Laboratory of Photochemistry, Department of Drug Sciences, University of Catania , Viale Andrea Doria 6, I-95125 Catania, Italy.
authors.forename: Noufal
authors.initials: N
authors.lastname: Kandoth
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kirejev
authors.forename: Sandra
authors.initials: S
authors.lastname: Monti
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
authors.forename: Marica B
authors.initials: MB
authors.lastname: Ericson
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sortino
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D004811:Epichlorohydrin / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry; D054833:Isoindoles; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000737:chemistry; D017785:Photons; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects; D026082:Singlet Oxygen / Q000737:chemistry / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017967:Zinc Compounds; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011108:Polymers; D017967:Zinc Compounds; D047392:beta-Cyclodextrins; D004811:Epichlorohydrin; C052159:Zn(II)-phthalocyanine; D026082:Singlet Oxygen; D009569:Nitric Oxide; C031215:betadex