PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer

Prashanth K.B. Nagesh; Nia R. Johnson; Vijaya K.N. Boya; Pallabita Chowdhury; Shadi F. Othman; Vahid Khalilzad-Sharghi; Bilal B. Hafeez; Aditya Ganju; Sheema Khan; Stephen W. Behrman; Nadeem Zafar; Subhash C. Chauhan; Meena Jaggi; Murali M. Yallapu

doi:10.1016/j.colsurfb.2016.03.071

PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer

Prashanth K.B. Nagesh, Nia R. Johnson, Vijaya K.N. Boya, Pallabita Chowdhury, Shadi F. Othman, Vahid Khalilzad-Sharghi, Bilal B. Hafeez, Aditya Ganju, Sheema Khan, Stephen W. Behrman, Nadeem Zafar, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

Biological Systems Engineering

Research output: Contribution to journal › Article › peer-review

109 Scopus citations

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.

Original language	English (US)
Pages (from-to)	8-20
Number of pages	13
Journal	Colloids and Surfaces B: Biointerfaces
Volume	144
DOIs	https://doi.org/10.1016/j.colsurfb.2016.03.071
State	Published - Aug 1 2016

Keywords

Drug delivery
Magnetic nanoparticles
Prostate cancer
Targeted delivery

ASJC Scopus subject areas

Biotechnology
Surfaces and Interfaces
Physical and Theoretical Chemistry
Colloid and Surface Chemistry

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Nagesh, P. K. B., Johnson, N. R., Boya, V. K. N., Chowdhury, P., Othman, S. F., Khalilzad-Sharghi, V., Hafeez, B. B., Ganju, A., Khan, S., Behrman, S. W., Zafar, N., Chauhan, S. C., Jaggi, M., & Yallapu, M. M. (2016). PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer. Colloids and Surfaces B: Biointerfaces, 144, 8-20. https://doi.org/10.1016/j.colsurfb.2016.03.071

Nagesh, PKB, Johnson, NR, Boya, VKN, Chowdhury, P, Othman, SF, Khalilzad-Sharghi, V, Hafeez, BB, Ganju, A, Khan, S, Behrman, SW, Zafar, N, Chauhan, SC, Jaggi, M & Yallapu, MM 2016, 'PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer', Colloids and Surfaces B: Biointerfaces, vol. 144, pp. 8-20. https://doi.org/10.1016/j.colsurfb.2016.03.071

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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.",

keywords = "Drug delivery, Magnetic nanoparticles, Prostate cancer, Targeted delivery",

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doi = "10.1016/j.colsurfb.2016.03.071",

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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.

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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JF - Colloids and Surfaces B: Biointerfaces

ER -

PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer

Abstract

Keywords

ASJC Scopus subject areas

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