DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Soyoung | ko |
dc.contributor.author | Lee, Yonghyun | ko |
dc.contributor.author | Kim, Hyungjun | ko |
dc.contributor.author | Lee, Dong Yun | ko |
dc.contributor.author | Jon, Sangyong | ko |
dc.date.accessioned | 2018-07-24T02:21:47Z | - |
dc.date.available | 2018-07-24T02:21:47Z | - |
dc.date.created | 2018-07-04 | - |
dc.date.created | 2018-07-04 | - |
dc.date.issued | 2018-06 | - |
dc.identifier.citation | BIOMACROMOLECULES, v.19, no.6, pp.2270 - 2277 | - |
dc.identifier.issn | 1525-7797 | - |
dc.identifier.uri | http://hdl.handle.net/10203/244004 | - |
dc.description.abstract | Despite growing interest in targeted cancer therapy with small molecule drug conjugates (SMDCs), the short half-life of these conjugates in blood associated with their small size has limited their efficacy in cancer therapy. In this report, we propose a new approach for improving the antitumor efficacy of SMDCs based on nanoparticle-assisted delivery. Ideally, a nanoparticle-based delivery vehicle would prolong the half-life of an SMDC in blood and then release it in response to stimuli in the tumor microenvironment (TME). In this study, PEGylated bilirubin-based nanoparticles (BRNPs) were chosen as an appropriate delivery carrier because of their ability to release drugs in response to TME-associated reactive oxygen species (ROS) through rapid particle disruption. As a model SMDC, ACUPA-SN38 was synthesized by linking the prostate-specific membrane antigen (PSMA)-targeting ligand, ACUPA, to the chemotherapeutic agent, SN38. ACUPA-SN38 was loaded into BRNPs using a film-formation and rehydration method. The resulting ACUPA-SN38@BRNPs exhibited ROS-mediated particle disruption and rapid release of the SMDC, resulting in greater cytotoxicity toward PSMA-overexpressing prostate cancer cells (LNCaP) than toward ROSunresponsive ACUPA-SN38@Liposomes. In a pharmacokinetic study, the circulation time of ACUPA-SN38@BRNP5 in blood was prolonged by approximately 2-fold compared with that of the SMDC-based micellar nanoparticles. Finally, ACUPA-SN38@BRNPs showed greater antitumor efficacy in a PSMA-overexpressing human prostate xenograft tumor model than SN38@BRNPs or the SMDC alone. Collectively, these findings suggest that BRNPs are a viable delivery carrier option for various cancer-targeting SMDCs that suffer from short circulation half-life and limited therapeutic efficacy. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.subject | MEMBRANE-ANTIGEN | - |
dc.subject | CELLS | - |
dc.subject | MICROENVIRONMENT | - |
dc.subject | INFLAMMATION | - |
dc.subject | PATHWAY | - |
dc.subject | DESIGN | - |
dc.subject | TUMORS | - |
dc.subject | SN38 | - |
dc.title | Bilirubin Nanoparticle-Assisted Delivery of a Small Molecule-Drug Conjugate for Targeted Cancer Therapy | - |
dc.type | Article | - |
dc.identifier.wosid | 000435226200049 | - |
dc.identifier.scopusid | 2-s2.0-85046541211 | - |
dc.type.rims | ART | - |
dc.citation.volume | 19 | - |
dc.citation.issue | 6 | - |
dc.citation.beginningpage | 2270 | - |
dc.citation.endingpage | 2277 | - |
dc.citation.publicationname | BIOMACROMOLECULES | - |
dc.identifier.doi | 10.1021/acs.biomac.8b00189 | - |
dc.contributor.localauthor | Jon, Sangyong | - |
dc.contributor.nonIdAuthor | Lee, Soyoung | - |
dc.contributor.nonIdAuthor | Lee, Yonghyun | - |
dc.contributor.nonIdAuthor | Kim, Hyungjun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | MEMBRANE-ANTIGEN | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | MICROENVIRONMENT | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | DESIGN | - |
dc.subject.keywordPlus | TUMORS | - |
dc.subject.keywordPlus | SN38 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.