Medway School of Science, Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, ME4 4TB Kent, United Kingdom.
Medway School of Science, Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, ME4 4TB Kent, United Kingdom; Centre for Innovation & Process Engineering Research, Chatham Maritime, ME4 4TB Kent, United Kingdom.
Int J Pharm. 2021 Apr 15;599:120416. doi: 10.1016/j.ijpharm.2021.120416. Epub 2021 Feb 27.
Prostate cancer is one of the prominent causes of cancer mortality in men all over the world and a challenge to treat. In this study, transferrin (Tf) bioconjugated solid lipid nanoparticles (SLNs) were developed and loaded with curcumin (CRC) for active targeting of prostate cancer cells. Curcumin is an anticancer agent, but its clinical applications are impeded due to the poor water solubility and bioavailability. Prepared blank Tf-SLNs showed minimal cytotoxicity while Tf-CRC-SLNs demonstrated significant in-vitro anti-proliferative activity compared to CRC-SLNs alone. Cellular uptake of Tf-CRC-SLNs were found to be significantly higher (p < 0.05/=0.01) compared to unconjugated SLNs or pure drug alone. Bioconjugated Tf-CRC-SLNs also showed improved early apoptotic and late apoptotic or early necrotic populations (6.4% and 88.9% respectively) to CRC-SLNs and CRC solution. Most importantly, in-vivo studies with Tf-CRC-SLNs in mice bearing prostate cancer revealed significant tumour regression (392.64 mm after 4 weeks, p < 0.001) compared to the control group. The findings of this work encourage future investigations and further in-vivo clinical studies on the potential of bioconjugated SLNs for cancer cure.
前列腺癌是全世界男性癌症死亡的主要原因之一,也是治疗的难点。在这项研究中,转铁蛋白(Tf)偶联的固体脂质纳米粒(SLNs)被开发出来,并负载姜黄素(CRC)以主动靶向前列腺癌细胞。姜黄素是一种抗癌药物,但由于其水溶性和生物利用度差,其临床应用受到限制。制备的空白 Tf-SLNs 表现出最小的细胞毒性,而 Tf-CRC-SLNs 与单独的 CRC-SLNs 相比,表现出显著的体外抗增殖活性。与未偶联的 SLNs 或纯药物相比,Tf-CRC-SLNs 的细胞摄取量明显更高(p<0.05/=0.01)。生物共轭 Tf-CRC-SLNs 还显示出对 CRC-SLNs 和 CRC 溶液的早期凋亡和晚期凋亡或早期坏死群体的改善(分别为 6.4%和 88.9%)。最重要的是,在携带前列腺癌的小鼠中进行的 Tf-CRC-SLNs 体内研究显示出与对照组相比肿瘤明显消退(第 4 周后为 392.64 mm,p<0.001)。这项工作的发现鼓励对用于癌症治疗的生物共轭 SLNs 的潜力进行未来的研究和进一步的体内临床研究。