title: Theranostic gas-generating nanoparticles for targeted ultrasound imaging and treatment of neuroblastoma.
abstract: The development of safe and efficient diagnostic/therapeutic agents for treating cancer in clinics remains challenging due to the potential toxicity of conventional agents. Although the annual incidence of neuroblastoma is not that high, the disease mainly occurs in children, a population vulnerable to toxic contrast agents and therapeutics. We demonstrate here that cancer-targeting, gas-generating polymeric nanoparticles are useful as a theranostic tool for ultrasound (US) imaging and treating neuroblastoma. We encapsulated calcium carbonate using poly(d,l-lactide-co-glycolide) and created gas-generating polymer nanoparticles (GNPs). These nanoparticles release carbon dioxide bubbles under acidic conditions and enhance US signals. When GNPs are modified using rabies virus glycoprotein (RVG) peptide, a targeting moiety to neuroblastoma, RVG-GNPs effectively accumulate at the tumor site and substantially enhance US signals in a tumor-bearing mouse model. Intravenous administration of RVG-GNPs also reduces tumor growth in the mouse model without the use of conventional therapeutic agents. This approach to developing theranostic agents with disease-targeting ability may provide useful strategy for the detection and treatment of cancers, allowing safe and efficient clinical applications with fewer side effects than may occur with conventional agents.
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea; Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Jangwook
authors.initials: J
authors.lastname: Lee
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Hyun-Su
authors.initials: HS
authors.lastname: Min
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Dong Gil
authors.initials: DG
authors.lastname: You
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea; Institute of Nano Science and Technology, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Taiyoun
authors.initials: T
authors.lastname: Rhim
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea; Institute of Nano Science and Technology, Hanyang University, Seoul 133-791, Republic of Korea. Electronic address: leeky@hanyang.ac.kr.
authors.forename: Kuen Yong
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D002119:Calcium Carbonate / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002245:Carbon Dioxide / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003952:Diagnostic Imaging; D006023:Glycoproteins / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use; D009447:Neuroblastoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D047368:Tumor Burden / Q000187:drug effects; D000069453:Ultrasonic Waves; D014764:Viral Proteins / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D006023:Glycoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; C583075:rabies virus glycoprotein peptide; D002245:Carbon Dioxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002119:Calcium Carbonate
keywords: Gas-generating nanoparticle; Neuroblastoma; Rabies virus glycoprotein; Theranostic system