title: pH-controlled gas-generating mineralized nanoparticles: a theranostic agent for ultrasound imaging and therapy of cancers.
abstract: We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO3) hybrid nanoparticles (DOX-CaCO3-MNPs) through a block copolymer templated in situ mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO2) bubbles and showed excellent echo persistence. In vivo results demonstrated that the DOX-CaCO3-MNPs generated CO2 bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO3-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO2 bubbles necessary for US contrast. The DOX-CaCO3-MNPs could also trigger the DOX release simultaneously with CO2 bubble generation at the acidic tumoral environment. The DOX-CaCO3-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers.
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology , Seoul 136-791, Republic of Korea.
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Min
authors.forename: Hyun Su
authors.initials: HS
authors.lastname: Min
authors.forename: Hong Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Park
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Yhee
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Oscar F
authors.initials: OF
authors.lastname: Silvestre
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Yu-Shik
authors.initials: YS
authors.lastname: Hwang
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
authors.forename: Sang Cheon
authors.initials: SC
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport; D002119:Calcium Carbonate / Q000737:chemistry*; D002245:Carbon Dioxide / Q000737:chemistry*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry*; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014463:Ultrasonography
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D002245:Carbon Dioxide; D004317:Doxorubicin; D002119:Calcium Carbonate
keywords: carbon dioxide; drug delivery; mineralization; nanobubble; theranostics; ultrasound