title: PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer.
abstract: Docetaxel (Dtxl) is currently the most common therapeutic option for prostate cancer (PC). However, adverse side effects and problems associated with chemo-resistance limit its therapeutic outcome in clinical settings. A targeted nanoparticle system to improve its delivery to and activity at the tumor site could be an attractive strategy for PC therapy. Therefore, the objective of this study was to develop and determine the anti-cancer efficacy of a novel docetaxel loaded, prostate specific membrane antigen (PSMA) targeted superparamagnetic iron oxide nanoparticle (SPION) (J591-SPION-Dtxl) formulation for PC therapy. Our results showed the SPION-Dtxl formulation exhibits an optimal particle size and zeta potential, which can efficiently be internalized in PC cells. SPION-Dtxl exhibited potent anti-cancer efficacy via induction of the expression of apoptosis associated proteins, downregulation of anti-apoptotic proteins, and inhibition of chemo-resistance associated protein in PC cell lines. J591-SPION-Dtxl exhibited a profound uptake in C4-2 (PSMA(+)) cells compared to PC-3 (PSMA(-)) cells. A similar targeting potential was observed in ex-vivo studies in C4-2 tumors but not in PC-3 tumors, suggesting its tumor specific targeting. Overall, this study suggests that a PSMA antibody functionalized SPION-Dtxl formulation can be highly useful for targeted PC therapy.
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Prashanth K B
authors.initials: PKB
authors.lastname: Nagesh
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Nia R
authors.initials: NR
authors.lastname: Johnson
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Vijaya K N
authors.initials: VKN
authors.lastname: Boya
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Pallabita
authors.initials: P
authors.lastname: Chowdhury
authors.affiliation: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Shadi F
authors.initials: SF
authors.lastname: Othman
authors.affiliation: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Vahid
authors.initials: V
authors.lastname: Khalilzad-Sharghi
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Bilal B
authors.initials: BB
authors.lastname: Hafeez
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Ganju
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Sheema
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Behrman
authors.affiliation: Department of Pathology, College of Medicine, University of Tennessee at Memphis, Memphis, TN, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Zafar
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address: mjaggi@uthsc.edu.
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address: myallapu@uthsc.edu.
authors.forename: Murali M
authors.initials: MM
authors.lastname: Yallapu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry*; D000077143:Docetaxel; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D058185:Magnetite Nanoparticles; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; C065507:ferumoxides
keywords: Drug delivery; Magnetic nanoparticles; Prostate cancer; Targeted delivery