title: Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes.
abstract: BACKGROUND
  Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide-co-glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP-mediated PSDT on MH7A synoviocytes.
  
  
  METHODS
  The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP-mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation.
  
  
  RESULTS
  The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP-mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP-mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavengerN-acetylcysteine.
  
  
  CONCLUSIONS
  Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP-mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase-transition nanoparticle-mediated PSDT in the future.
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University; Department of Ultrasound, Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University; State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Ultrasound, Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University.
authors.forename: Shenyin
authors.initials: S
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001672:Biocompatible Materials; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005347:Fibroblasts / Q000473:pathology; D005434:Flow Cytometry; D005466:Fluorocarbons / Q000737:chemistry; D006801:Humans; D007208:Indocyanine Green / Q000008:administration & dosage; D019344:Lactic Acid / Q000737:chemistry; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010100:Oxygen / Q000008:administration & dosage; D010778:Photochemotherapy / Q000379:methods*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000070918:Synoviocytes / Q000187:drug effects* / Q000378:metabolism; D010420:Pentanes
chemical_list: D001672:Biocompatible Materials; D005466:Fluorocarbons; D007208:Indocyanine Green; D019344:Lactic Acid; D010100:Oxygen; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C008806:perfluoropentane; D010420:Pentanes
keywords: apoptosis; indocyanine green; multifunctional nanoparticles; reactive oxygen species; synoviocytes