TY - JOUR
T1 - PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer
AU - Nagesh, Prashanth K.B.
AU - Johnson, Nia R.
AU - Boya, Vijaya K.N.
AU - Chowdhury, Pallabita
AU - Othman, Shadi F.
AU - Khalilzad-Sharghi, Vahid
AU - Hafeez, Bilal B.
AU - Ganju, Aditya
AU - Khan, Sheema
AU - Behrman, Stephen W.
AU - Zafar, Nadeem
AU - Chauhan, Subhash C.
AU - Jaggi, Meena
AU - Yallapu, Murali M.
N1 - Funding Information:
This work was supported by a K22 award from the NIH (K22CA174841 to MMY). This work was also partially supported by the National Institutes of Health (R01 CA142736 to SCC and U01 CA162106 to SCC and MJ), and the College of Pharmacy Dean's Seed and Instrument Grant(s) of the University of Tennessee Health Science Center (to SCC, MJ and MMY). The authors wish to thank Cathy Christopherson for editorial assistance.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Drug delivery
KW - Magnetic nanoparticles
KW - Prostate cancer
KW - Targeted delivery
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U2 - 10.1016/j.colsurfb.2016.03.071
DO - 10.1016/j.colsurfb.2016.03.071
M3 - Article
C2 - 27058278
AN - SCOPUS:84962158502
SN - 0927-7765
VL - 144
SP - 8
EP - 20
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
ER -