Nanomedicine & Nanobiotechnology Lab, Department of Biosciences, Integral University, Lucknow, India.
Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abduaziz University, Al-kharj, Saudi Arabia.
PLoS One. 2022 Aug 26;17(8):e0272396. doi: 10.1371/journal.pone.0272396. eCollection 2022.
Prostate cancer is the second-deadliest tumor in men all over the world. Different types of drugs with various delivery systems and pathways were developed, but no one showed prominent results against cancer. Meanwhile, nanoparticles have shown good results against cancer. Therefore, in the given study, citrate mediated synthesized gold nanoparticles (CtGNPs) with immobilized survivin antibodies (SvGNPs) were bioconjugated to the substantially potent drug abiraterone (AbSvGNPs) to develop as a combinatorial therapeutic against prostate cancer. The AbSvGNPs are made up of CtGNPs, survivin antibodies, and abiraterone. The selected drug abiraterone (Abira) possesses exceptionally good activity against prostate cancer, but cancer cells develop resistance against this drug and it also poses several severe side effects. Meanwhile, survivin antibodies were used to deliver AbSvGNPs specifically into cancer cells by considering survivin, an anti-apoptotic overexpressed protein in cancer cells, as a marker. The survivin antibodies have also been used to inhibit cancer cells as an immunotherapeutic agent. Similarly, CtGNPs were discovered to inhibit cancer cell proliferation via several transduction pathways. The given bioconjugated nanoparticles (AbSvGNPs) were found to be substantially effective against prostate cancer with an IC50 of 11.8 and 7.3 μM against DU145 and PC-3 cells, respectively. However, it was found safe against NRK and showed less than 25% cytotoxicity up to 20μM concentration. The as-synthesized nanoparticles CtGNPs, SvGNPs, and AbSvGNPs were characterized by several physical techniques to confirm their synthesis, whereas the immobilization of survivin antibodies and bioconjugation of Abira was confirmed by UV-visible spectroscopy, DLS, TEM, FTIR, and zeta-potential. The anticancer potential of AbSvGNPs was determined by MTT, DAPI, ROS, MITO, TUNEL ASSAY, and caspase-3 activity against DU145 and PC3 cells.
前列腺癌是全世界男性第二大致命肿瘤。已经开发出了具有不同传递系统和途径的多种类型的药物,但没有一种药物对癌症有显著疗效。与此同时,纳米颗粒在抗癌方面显示出了良好的效果。因此,在本研究中,柠檬酸介导合成的金纳米颗粒(CtGNPs)与固定化的survivin 抗体(SvGNPs)被生物偶联到具有强大功效的药物阿比特龙(AbSvGNPs)上,以开发出针对前列腺癌的联合治疗方法。AbSvGNPs 由 CtGNPs、survivin 抗体和阿比特龙组成。所选药物阿比特龙(Abira)对前列腺癌具有非常好的活性,但癌细胞会对这种药物产生耐药性,而且它还会产生一些严重的副作用。同时,survivin 抗体被用于通过将 survivin(癌细胞中过度表达的抗凋亡蛋白)作为标志物将 AbSvGNPs 特异性递送到癌细胞中。survivin 抗体也被用作免疫治疗剂来抑制癌细胞。同样,CtGNPs 被发现通过几种转导途径抑制癌细胞增殖。所研究的生物偶联纳米颗粒(AbSvGNPs)对前列腺癌具有显著的抑制作用,其对 DU145 和 PC-3 细胞的 IC50 分别为 11.8 和 7.3 μM。然而,它对 NRK 表现出安全性,在 20 μM 浓度下的细胞毒性小于 25%。所合成的纳米颗粒 CtGNPs、SvGNPs 和 AbSvGNPs 通过几种物理技术进行了表征,以确认其合成,而 survivin 抗体的固定化和 Abira 的生物偶联则通过紫外可见光谱、DLS、TEM、FTIR 和zeta-电位进行了确认。通过 MTT、DAPI、ROS、MITO、TUNEL 分析和 caspase-3 活性测定,研究了 AbSvGNPs 对 DU145 和 PC3 细胞的抗癌潜力。