Survivin-targeted nanomedicine for increased potency of abiraterone and enzalutamide against prostate cancer

Abu Baker; Asad Syed; Mohamed Mohany; Abdallah M Elgorban; Mohd Sajid Khan; Salim S Al-Rejaie

doi:10.1016/j.ejpb.2023.10.005

Survivin-targeted nanomedicine for increased potency of abiraterone and enzalutamide against prostate cancer

Eur J Pharm Biopharm. 2023 Nov:192:88-111. doi: 10.1016/j.ejpb.2023.10.005. Epub 2023 Oct 4.

Authors

Abu Baker¹, Asad Syed², Mohamed Mohany³, Abdallah M Elgorban⁴, Mohd Sajid Khan¹, Salim S Al-Rejaie⁵

Affiliations

¹ Nanomedicine & Nanobiotechnology Lab, Department of Biosciences, Integral University, Lucknow 226026 India.
² Department of Botany and Microbiology, College of Science, King Saud University, P.O. 2455, Riyadh 11451, Saudi Arabia.
³ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. 55760, Riyadh 11451, Saudi Arabia.
⁴ Center of Excellence in Biotechnology Research, King Saud University, Riyadh, Saudi Arabia.
⁵ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. 55760, Riyadh 11451, Saudi Arabia. Electronic address: rejaie@ksu.edu.sa.

PMID: 37797680
DOI: 10.1016/j.ejpb.2023.10.005

Abstract

Prostate cancer is the leading and most aggressive cancer around the world, several therapeutic approaches have emerged but none have achieved the satisfactory result. However, these therapeutic approaches face many challenges related to their delivery to target cells, including their in vivo decay, the limited uptake by target cells, the requirements for nuclear penetration (in some cases), and the damage caused to healthy cells. These barriers can be avoided by effective, targeted, combinatorial approaches, with minimal side effects, which are being investigated for the treatment of cancer. Here, we developed a combinatorial nanomedicine comprising abiraterone and enzalutamide bioconjugated survivin-encapsulated gold nanoparticles (AbEzSvGNPs) for targeted therapy of prostate cancer. AbEzSvGNPs were characterized by different biophysical techniques such as UV visible spectroscopy, dynamic light scattering, zeta potential, transmission electron microscope, and Fourier transform infrared spectroscopy. Interestingly, the effect of abiraterone, enzalutamide and surviving encapsulated gold nanoparticles was found to be synergistic in nature in AbEzSvGNPs against DU 145 (IC₅₀ = 4.21 µM) and PC-3 (IC_{50 =} 5.58 µM) cells and their potential was observed to be greatly enhanced as compared with the combined effect of the drugs (abiraterone and enzalutamide) in their free form. Furthermore, AbEzSvGNPs were found to be highly safe and did not exhibit significant cytotoxicity against normal rat kidney cells. The observed effects of AbEzSvGNPs involved the modulation of different signaling pathways in prostate cancer cells. This delivery system employed non-androgen receptor-dependent delivery of abiraterone and enzalutamide. The anionic AbEzSvGNPs delivered abiraterone and enzalutamide unaltered into the nucleus through caveolae mediated internalization to act nonspecifically on DNA; internalization of the anionic nanoparticles into the cytoplasm was also observed via other routes. AbEzSvGNPs synthesized and evaluated in this study are promising candidates for prostate cancer therapy.

Keywords: Abiraterone; Enzalutamide; GNPs; Prostate cancer; Survivin.

MeSH terms

Gold
Humans
Male
Metal Nanoparticles*
Nanomedicine
Prostatic Neoplasms, Castration-Resistant* / drug therapy
Survivin

Substances

abiraterone
enzalutamide
Survivin
Gold