FigsharePub Date : 2018-05-04DOI: 10.1021/acs.biomac.8b00189.s001
Soyoung Lee (36756), Yonghyun Lee (5175587), Hyungjun Kim (533683), Dong Yun Lee (1398103), Sangyong Jon (1343082)
{"title":"Bilirubin Nanoparticle-Assisted Delivery of a SmallnMolecule-Drug Conjugate for Targeted Cancer Therapy","authors":"Soyoung Lee (36756), Yonghyun Lee (5175587), Hyungjun Kim (533683), Dong Yun Lee (1398103), Sangyong Jon (1343082)","doi":"10.1021/acs.biomac.8b00189.s001","DOIUrl":"https://doi.org/10.1021/acs.biomac.8b00189.s001","url":null,"abstract":"Despite growing interestnin targeted cancer therapy with smallnmolecule drug conjugates (SMDCs), the short half-life of these conjugatesnin blood associated with their small size has limited their efficacynin cancer therapy. In this report, we propose a new approach for improvingnthe antitumor efficacy of SMDCs based on nanoparticle-assisted delivery.nIdeally, a nanoparticle-based delivery vehicle would prolong the half-lifenof an SMDC in blood and then release it in response to stimuli innthe tumor microenvironment (TME). In this study, PEGylated bilirubin-basednnanoparticles (BRNPs) were chosen as an appropriate delivery carriernbecause of their ability to release drugs in response to TME-associatednreactive oxygen species (ROS) through rapid particle disruption. Asna model SMDC, ACUPA-SN38 was synthesized by linking the prostate-specificnmembrane antigen (PSMA)-targeting ligand, ACUPA, to the chemotherapeuticnagent, SN38. ACUPA-SN38 was loaded into BRNPs using a film-formationnand rehydration method. The resulting ACUPA-SN38@BRNPs exhibited ROS-mediatednparticle disruption and rapid release of the SMDC, resulting in greaterncytotoxicity toward PSMA-overexpressing prostate cancer cells (LNCaP)nthan toward ROS-unresponsive ACUPA-SN38@Liposomes. In a pharmacokineticnstudy, the circulation time of ACUPA-SN38@BRNPs in blood was prolongednby approximately 2-fold compared with that of the SMDC-based micellarnnanoparticles. Finally, ACUPA-SN38@BRNPs showed greater antitumornefficacy in a PSMA-overexpressing human prostate xenograft tumor modelnthan SN38@BRNPs or the SMDC alone. Collectively, these findings suggestnthat BRNPs are a viable delivery carrier option for various cancer-targetingnSMDCs that suffer from short circulation half-life and limited therapeuticnefficacy.","PeriodicalId":523526,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147917719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}