318 NANOPARTICLE-MEDIATED DELIVERY OF IMAGING AND THERAPEUTIC AGENTS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2012318 NANOPARTICLE-MEDIATED DELIVERY OF IMAGING AND THERAPEUTIC AGENTS Dhruba Bharali, Sudha Thangirala, Himanshu Aggarwal, Murat Yalcin, Ahmed Elsaid, Huadong Cui, Tipu Nazeer, Shaker Mousa, and Badar Mian Dhruba BharaliDhruba Bharali Rensselaer, NY More articles by this author , Sudha ThangiralaSudha Thangirala Rensselaer, NY More articles by this author , Himanshu AggarwalHimanshu Aggarwal Albany, NY More articles by this author , Murat YalcinMurat Yalcin Rensselaer, NY More articles by this author , Ahmed ElsaidAhmed Elsaid Rensselaer, NY More articles by this author , Huadong CuiHuadong Cui Rensselaer, NY More articles by this author , Tipu NazeerTipu Nazeer Albany, NY More articles by this author , Shaker MousaShaker Mousa Rensselaer, NY More articles by this author , and Badar MianBadar Mian Albany, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.378AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nanoparticle-based technology has shown promising results in increasing the delivery of drugs to tumor sites in order to reduce the dose-related toxicity through the use of passive targeting. The use of active targeting of tumors, using tumor specific targets, is needed in order to enhance the accumulation of imaging or therapeutic agents directly at the tumor site. We sought to determine the feasibility and efficacy of biodegradable, poly (lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) for targeted delivery of chemotherapeutic drugs using CD24 as a target (which has increased expression in androgen independent cell lines used below). METHODS We synthesized multi-functional PLGA-PEG nanoformulations encapsulating an imaging agent (fluorescent dye Alexa Flour 488 or Cy-5) and/or docetaxel, with and without conjugation to anti-CD24 antibody. Androgen independent cells, including a variant of LNcaP cells, LNCap-AI, and PC3-M cells were used for in vitro targeting and uptake studies. PC3-M cells, after luciferase transfection, were orthotopically implanted in the nude mice prostate and mice treated with drug alone and with several nanoformulations including those with or without the targeting moiety to determine the specificity of drug delivery and tumor response. The animals were serially imaged using fluorescence to track the distribution of the nanoparticles and bioluminescence imaging to study tumor shrinkage using In Vivo Imaging system. RESULTS In vitro studies using fluorescence imaging demonstrated significantly enhanced uptake of CD24 conjugated nanoparticles by both cell lines at 1,2 and 4 hours. Significant decrease (75-300%)in the number of viable cells was noted in the group treated with anti-CD24 conjugated nanoparticles, despite much lower drug doses in the targeted NPs groups (10-50 nanomolar) when compared to docetaxel alone despite much higher dose (1 micromolar) in both cell lines. In the orthotopic prostate cancer model, the CD24-conjugated NPs carrying fluorescent probe demonstrated enhanced accumulation specifically at the tumor site while NPs carrying docetaxel showed a significantly increased accumulation (10-fold) of docetaxel. Similarly, NPs encapsulating docetaxel inhibited tumor growth as evident by reduced bioluminescent signal intensity and tumor weights. CONCLUSIONS Biodegradable NPs have the potential to deliver therapeutic and imaging agents in a targeted fashion. These formulations can carry multiple targeting and therapeutic molecules to enhance the anti-tumor effects at lower doses and toxicity. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e129 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dhruba Bharali Rensselaer, NY More articles by this author Sudha Thangirala Rensselaer, NY More articles by this author Himanshu Aggarwal Albany, NY More articles by this author Murat Yalcin Rensselaer, NY More articles by this author Ahmed Elsaid Rensselaer, NY More articles by this author Huadong Cui Rensselaer, NY More articles by this author Tipu Nazeer Albany, NY More articles by this author Shaker Mousa Rensselaer, NY More articles by this author Badar Mian Albany, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...