{"created":"2023-05-15T14:56:03.093555+00:00","id":76122,"links":{},"metadata":{"_buckets":{"deposit":"505357bc-d28d-438d-81c5-3e126416cf7a"},"_deposit":{"created_by":1,"id":"76122","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"76122"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00076122","sets":["10:28"]},"author_link":["764867","764873","764869","764866","764875","764871","764872","764874","764870","764868"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2019-05-27","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Objectives: Photothermal therapy (PTT) employs the heat generated from the absorbed optical energy by light-absorbing agents accumulated in the tumor to ablate tumor cells. Photodynamic therapy (PDT) is a clinically approved, minimally invasive technique that can exert a procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Black phosphorus quantum dots (BPQDs), a type of newly developed nanomaterial material, have attracted tremendous research interest owing to their distinctive physical/chemical properties [1]. BP has an excellent photothermal effect under near-infrared (NIR) irradiation, which gives a high photothermal conversion efficiency as high as 28%. BPs possess excellent biocompatibility and biodegradability properties under physiological conditions [2]. Here, we aim to develop a theranostic platform based on the radioisotope-loading BPQDs. In order to maximize the tumor targeting effect, two peptides were conjugated to the surface of QDs, which can sequentially recognize the tumor infiltrated vessels and tumor cell membrane receptor, thereby achieve maximum accumulation in the tumor site.\n\nMethods: Chelator-free labeling of BP with copper-64 and nanocomplex forming: 64Cu produced in house was diluted with HEPES buffer and mixed with BPQDs. The reaction was conducted at room temperature for 10 min with constant shaking. The resulting BPQD@64Cu was easily collected by centrifugation. This nanocomplex was resuspended in buffer and the beta hairpin peptide was added. After incubation, peptide-modified BP@64Cu nanocomplex as a final product was obtained by filtration. \nSurface peptide ligands conjugation: Two peptide ligands, VEGF 125-136 binds to vascular endothelial growth factor (VEGF) and cyclo-RGDyC binds to integrin av3 respectively, were conjugated to poly(oxyethylene) via a 3+2 yne-azide click reaction and a maleimide-thiol reaction, respectively. The peptides-modified PEG was complexed with BPQD@64Cu for 2 hours with constant stirring. The final BPQD@64Cu@PEG-VEGF/RGD was formulated by centrifugation.\nIn vitro cellular uptake and in vivo PET imaging: The cellular uptake mechanism was investigated by fluorescent imaging and radioactivity experiment. The blocking assay was also performed. The release kinetics of 64Cu and peptide from the nanocomplex was studied at different pH values. The in vitro cell viability, the PPT efficiency, and PDT effect were carefully evaluated. PET imaging was performed in B6F10 bearing Balb/c nude mice. Ex vivo biodistribution in the major organs of tumor mice was also performed. Finally, the anti-cancer therapy by PTT and PDT was conducted.\n\nResults: 64Cu ions bound tightly to the BPQDs. The BPQD@64Cu@PEG-VEGF/RGD nanocomplex showed effective internalization by the cancer cells and can be blocked by either VEGF or RGD peptides, demonstrating the peptide ligand-mediated active targeting effects. PET imaging results indicated that the 64Cu-nanocomplex was efficiently accumulated in the tumor site. Moreover, this nanocomplex showed significant tumor growth inhibition in the mice model. \n\nConclusion: The BPQD@64Cu@PEG-VEGF/RGD nanocomplex is a promising theranostic platform for PET imaging-guided cancer PTT/PDT therapy. Further preclinical biosafety study of the nanoparticles will be studied.\n\nReferences: [1] K. Hu et al. Small, 2018, 14, 1801701. [2] K Hu et al. J. Mater. Chem. B. 2018, 5, 5433-5440.\n","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"ISRS2019","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Kuan, Hu"}],"nameIdentifiers":[{"nameIdentifier":"764866","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Xie, Lin"}],"nameIdentifiers":[{"nameIdentifier":"764867","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hanyu, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"764868","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding"}],"nameIdentifiers":[{"nameIdentifier":"764869","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ming-Rong, Zhang"}],"nameIdentifiers":[{"nameIdentifier":"764870","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kuan, Hu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"764871","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Xie, Lin","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"764872","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hanyu, Masayuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"764873","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"764874","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ming-Rong, Zhang","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"764875","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Peptide modified and radiometals loaded BP quantum dots for targeted PET imaging-guided tumor photothermal and photodynamic therapy  ","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Peptide modified and radiometals loaded BP quantum dots for targeted PET imaging-guided tumor photothermal and photodynamic therapy  "}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-06-03"},"publish_date":"2019-06-03","publish_status":"0","recid":"76122","relation_version_is_last":true,"title":["Peptide modified and radiometals loaded BP quantum dots for targeted PET imaging-guided tumor photothermal and photodynamic therapy  "],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-16T00:37:26.508240+00:00"}