Nanomedicine & Nanobiotechnology Lab, Department of Biosciences, Integral University, Lucknow 226026 India.
Department of Botany and Microbiology, College of Science, King Saud University, P.O. 2455, Riyadh 11451, Saudi Arabia.
Eur J Pharm Biopharm. 2023 Nov;192:88-111. doi: 10.1016/j.ejpb.2023.10.005. Epub 2023 Oct 4.
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 (IC = 4.21 µM) and PC-3 (IC 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.
前列腺癌是全球范围内最常见和最具侵袭性的癌症之一，已经出现了几种治疗方法，但都没有达到令人满意的效果。然而，这些治疗方法在递送到靶细胞时面临许多挑战，包括体内衰减、靶细胞摄取有限、核穿透要求（在某些情况下）以及对健康细胞的损伤。这些障碍可以通过有效、靶向、组合的方法来避免，这些方法具有最小的副作用，正在被研究用于癌症治疗。在这里，我们开发了一种组合纳米医学，包括阿比特龙和恩杂鲁胺偶联的survivin 包封金纳米粒子（AbEzSvGNPs），用于前列腺癌的靶向治疗。AbEzSvGNPs 通过不同的生物物理技术进行了表征，如紫外可见光谱、动态光散射、Zeta 电位、透射电子显微镜和傅里叶变换红外光谱。有趣的是，发现阿比特龙、恩杂鲁胺和包裹的金纳米粒子的协同作用在 AbEzSvGNPs 中是本质上的，对 DU 145（IC = 4.21 µM）和 PC-3（IC 5.58 µM）细胞的效果，并且与游离药物（阿比特龙和恩杂鲁胺）的联合作用相比，其潜力大大增强。此外，AbEzSvGNPs 被发现非常安全，对正常大鼠肾细胞没有显著的细胞毒性。AbEzSvGNPs 的观察到的效果涉及到前列腺癌细胞中不同信号通路的调节。这种给药系统采用非雄激素受体依赖性的阿比特龙和恩杂鲁胺的给药。带负电荷的 AbEzSvGNPs 通过 caveolae 介导的内吞作用将阿比特龙和恩杂鲁胺未改变地递送到细胞核中，从而对 DNA 产生非特异性作用；还观察到带负电荷的纳米粒子通过其他途径进入细胞质的内吞作用。在这项研究中合成和评估的 AbEzSvGNPs 是治疗前列腺癌的有前途的候选药物。
