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联合疗法:用多糖-前药复合物功能化金纳米笼靶向CD133+胶质瘤干细胞样细胞

Combinatorial Therapy: Targeting CD133+ Glioma Stem-like Cells with a Polysaccharide-Prodrug Complex Functionalised Gold Nanocages.

作者信息

Raveendran Sreejith, Giram Amit, Elmi Mehrnaz, Ray Santanu, Ireson Christopher, Alavijeh Mo, Savina Irina N

机构信息

School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Lewes Road, Moulsecoomb, Brighton BN2 4GJ, UK.

Pharmidex Pharmaceutical Services Limited, 167-169 Great Portland Street, Fifth Floor, London W1W 5PF, UK.

出版信息

Biomedicines. 2024 Apr 23;12(5):934. doi: 10.3390/biomedicines12050934.

Abstract

Cancer treatments are advancing to harness the body's immune system against tumours, aiming for lasting effects. This progress involves combining potent chemotherapy drugs with immunogens to kill cancer cells and trigger lasting immunity. Developing new prodrugs that integrate both chemotherapy and immune-boosting elements could significantly improve anticancer outcomes by activating multiple mechanisms to kill cancer cells. While bacterial polysaccharides are typically not used in therapy due to their immune-stimulating properties, we propose a safe application of an extremophilic bacterial polysaccharide, Mauran (MR), modified with the anticancer drug 5-fluorouracil (5FU) to create a novel prodrug. This obtained prodrug, chloracetyl-MR-5FU, is specifically targeted using gold nanocages to CD133+ glioma cells. Test results have shown a high encapsulation efficiency of the drug during the polysaccharide modification process; its anticancer activity was demonstrated in vitro and the release of the prodrug was demonstrated in ex vivo studies.

摘要

癌症治疗正在不断进步,利用人体免疫系统对抗肿瘤,目标是实现持久疗效。这一进展包括将强效化疗药物与免疫原相结合,以杀死癌细胞并触发持久免疫。开发同时整合化疗和免疫增强元素的新型前药,通过激活多种机制杀死癌细胞,可显著改善抗癌效果。虽然细菌多糖因其免疫刺激特性通常不用于治疗,但我们提出一种安全应用的方法,即对极端嗜热细菌多糖毛兰多糖(MR)进行修饰,使其与抗癌药物5-氟尿嘧啶(5FU)结合,从而创造一种新型前药。通过金纳米笼将这种得到的前药氯乙酰基-MR-5FU特异性靶向CD133+胶质瘤细胞。测试结果表明,在多糖修饰过程中药物的包封效率很高;其抗癌活性在体外得到了证实,前药的释放也在离体研究中得到了证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb7f/11117750/215c3a20a8ca/biomedicines-12-00934-g002.jpg

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