title: HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy.
abstract: This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic.
authors.affiliation: State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P. R. China.
authors.forename: Sijing
authors.initials: S
authors.lastname: Yan
authors.affiliation: Ultrasound department of Second Hospital Affiliated to Chongqing Medical University, Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing 400010, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P. R. China.
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Ultrasound department of First Hospital Affiliated to Chongqing Medical University, Chongqing 400016, P. R. China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: He
authors.affiliation: Second Affiliated Hospital of Chongqing Medical University &Chongqing Key Laboratory of Ultrasound Molecular Imaging, 400016, P. R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Xu
authors.affiliation: Ultrasound department of First Hospital Affiliated to Chongqing Medical University, Chongqing 400016, P. R. China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Second Affiliated Hospital of Chongqing Medical University &Chongqing Key Laboratory of Ultrasound Molecular Imaging, 400016, P. R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P. R. China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Zou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000074059:Extracorporeal Shockwave Therapy / Q000379:methods*; D005260:Female; D006415:Hematoporphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy; D061088:Photoacoustic Techniques / Q000379:methods*; D014463:Ultrasonography / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D003287:Contrast Media; D006415:Hematoporphyrins; C494379:hematoporphyrin monomethyl ether