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PSMA 偶联组合脂质体制剂包封染料木黄酮和白花丹醌诱导前列腺癌细胞凋亡。

PSMA conjugated combinatorial liposomal formulation encapsulating genistein and plumbagin to induce apoptosis in prostate cancer cells.

机构信息

Department of Urology, Second Division of The First Hospital of Jilin University, 3302 Jilin Rd, Changchun, 130031, Jilin, People's Republic of China.

Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, 218 Ziqiang Rd, Changchun, 130041, Jilin, People's Republic of China.

出版信息

Colloids Surf B Biointerfaces. 2021 Jul;203:111723. doi: 10.1016/j.colsurfb.2021.111723. Epub 2021 Mar 26.

DOI:10.1016/j.colsurfb.2021.111723
PMID:33839474
Abstract

Although the biomedical sciences have achieved tremendous success in developing novel approaches to managing prostate cancer, this disease remains one of the major health concerns among men worldwide. Liposomal formulations of single drugs have shown promising results in cancer treatment; however, the use of multi drugs has shown a better therapeutic index than individual drugs. The identification of cancer-specific receptors has added value to design targeted drug delivering nanocarriers. We have developed genistein and plumbagin co-encapsulating liposomes (∼120 nm) with PSMA specific antibodies to target prostate cancer cells selectively in this work. These liposomes showed >90 % decrease in PSMA expressing prostate cancer cell proliferation without any appreciable toxicity to healthy cells and human red blood cells. Release of plumbagin and genistein was found to decrease the expression of PI3/AKT3 signaling proteins and Glut-1 receptors (inhibited glucose uptake and metabolism), respectively. The decrease in migration potential of cells and induced apoptosis established the observed anti-proliferative effect in prostate cancer cell lines. The discussed strategy of developing novel, non-toxic, and PSMA specific antibody conjugated liposomes carrying genistein and plumbagin drugs may also be used for encapsulating other drugs and inhibit the growth of different types of cancers.

摘要

尽管生物医学科学在开发治疗前列腺癌的新方法方面取得了巨大成功,但这种疾病仍然是全球男性健康的主要关注点之一。单药脂质体制剂在癌症治疗中显示出了有希望的结果,但多药联合使用比单一药物具有更好的治疗指数。对癌症特异性受体的鉴定为设计靶向药物输送纳米载体增添了价值。在这项工作中,我们开发了载有 PSMA 特异性抗体的同时包封染料木黄酮和白花丹醌的脂质体(约 120nm),以选择性地靶向前列腺癌细胞。这些脂质体显示出对表达 PSMA 的前列腺癌细胞增殖的抑制率超过 90%,而对健康细胞和人红细胞没有明显的毒性。发现释放的白花丹醌和染料木黄酮分别降低了 PI3/AKT3 信号蛋白和 Glut-1 受体(抑制葡萄糖摄取和代谢)的表达。细胞迁移能力的降低和诱导的细胞凋亡证实了对前列腺癌细胞系的观察到的抗增殖作用。所讨论的开发新型、无毒、PSMA 特异性抗体偶联脂质体载药的策略,也可以用于封装其他药物并抑制不同类型癌症的生长。

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