Noble Amanda R, Akkad Saeed, Yates Nicholas D J, Jeffries James M, Signoret Nathalie, Fascione Martin A
Department of Chemistry, University of York Heslington York YO10 5DD UK
Hull York Medical School, University of York York YO10 5DD UK
RSC Adv. 2024 Jul 29;14(33):23796-23801. doi: 10.1039/d4ra03640a. eCollection 2024 Jul 26.
Prostate cancer is the most common cancer in men in the UK with over 50 000 new cases diagnosed each year and although therapeutic advances in surgery, anti-androgens, radio- and chemotherapy have increased survival rates, there still remains a need for new treatments to combat the most aggressive forms of the disease. Gene therapy offers promise as an alternative approach but is reliant on selective targeting to the cancer cell surface. Herein we describe the novel construction of a prostate specific membrane antigen (PSMA) binding bioconjugate-polyplex, based on a glutamate-urea peptide scaffold using 'click' chemistry, which we demonstrate is capable of targeted delivery of a GFP gene to PSMA overexpressing prostate cancer cells, and therefore may have potential future application as part of a prostate cancer gene delivery therapy.
前列腺癌是英国男性中最常见的癌症,每年有超过5万例新病例被诊断出来。尽管手术、抗雄激素、放疗和化疗等治疗方法的进步提高了生存率,但仍需要新的治疗方法来对抗这种疾病最具侵袭性的形式。基因治疗有望成为一种替代方法,但依赖于对癌细胞表面的选择性靶向。在此,我们描述了一种基于谷氨酸-尿素肽支架,利用“点击”化学构建的新型前列腺特异性膜抗原(PSMA)结合生物共轭物-多聚体,我们证明它能够将绿色荧光蛋白(GFP)基因靶向递送至PSMA过表达的前列腺癌细胞,因此作为前列腺癌基因递送治疗的一部分可能具有潜在的未来应用价值。