基于氧化石墨烯的锌离子PSMA靶向传送体系用于前列腺癌治疗的研究

Zinc is an essential trace element that serves as an important factor in various physiological and biochemical circumstances. In humans, normal prostate epithelial cells accumulate the highest levels of zinc in any soft tissue of the body. Prostate carcinogenesis involves the transformation of zinc-accumulating normal epithelial cells into malignant cells, which do not accumulate zinc. The loss of the unique ability of the prostate to retain normal intracellular levels of zinc may be an important factor in the development and progression of prostate cancer..Numerous studies suggest that increased zinc intake might protect against progression of prostatic malignancy. However, there are limited reports about zinc ion and related preparations used in the treatment of prostate cancer. The main reasons restricting the application of zinc ions in the treatment of prostate cancer are the poor targeting and the low efficiency of zinc ionophores. Therefore, We intend to (1) construct a new zinc ions prostate cancer targeted delivery system with graphene oxide as a carrier, prostate specific membrane antigen (PSMA) to targets, PSMA specific aptamer A10-3.2 for targeted head .(2) through covalent modifications, nuclide markers and the experiments in vivo and in vitro test the stability, hemolytic, transmission efficiency, release rate, cell toxicity, security, distribution and metabolism of the delivery system, and to explore its effect on the treatment of prostate cancer in nude mice model. This project from the subjects of nanomaterials, biochemistry and molecular biology explored the application of zinc ions in the treatment of prostate cancer to provide theoretical basis and experimental base, and to open up new ideas.

锌是人体重要的微量元素，体内含锌量最高的器官是前列腺，而前列腺组织恶变过程中则失去积累锌的能力。包括本课题组在内的多项研究表明，增加锌离子的浓度能够抑制前列腺癌细胞的增殖、侵袭与转移，并诱导凋亡，提示锌离子具有显著的抗癌作用。然而目前尚缺乏锌离子及相关制剂应用于前列腺癌治疗的报道。现有的锌离子载体传送效率较低，靶向性差，是制约锌离子应用于前列腺癌治疗的主要原因。针对以上问题，本项目拟①构建新型的以氧化石墨烯为载体，前列腺特异性膜抗原PSMA为作用靶点，PSMA特异性适体A10-3.2为靶向头基的锌离子前列腺癌靶向传送体系。②通过共价修饰、核素标记与体内外实验检测传送体系的稳定性、溶血性、传递效率、释放率、细胞毒性、动物体内的安全性、分布及代谢等，探索其对前列腺癌裸鼠模型的治疗效果。本项目从纳米材料、生物化学与分子生物学角度为锌离子在前列腺癌治疗中的应用提供理论依据与实验基础，开辟新的思路。