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通过包裹脑靶向肽负载替莫唑胺的仿生纳米载体用于靶向给药系统,以促进胶质母细胞瘤细胞的抗癌作用。

Biomimetic nanocarriers loaded with temozolomide by cloaking brain-targeting peptides for targeting drug delivery system to promote anticancer effects in glioblastoma cells.

作者信息

Chen Huaming, Wang Yunhong, Wang Hai, Zhang Kun, Liu Yunfei, Li Qiangfeng, Li Chengli, Wen Zhonghui, Chen Ziyu

机构信息

Department of Neurosurgery, Pu'er People's Hospital, Pu'er, 665099, China.

Department of Emergency, Pu'er People's Hospital, Pu'er, 665099, China.

出版信息

Heliyon. 2024 Mar 15;10(7):e28256. doi: 10.1016/j.heliyon.2024.e28256. eCollection 2024 Apr 15.

Abstract

Glioma is the leading cancer of the central nervous system (CNS). The efficacy of glioma treatment is significantly hindered by the presence of the blood-brain barrier (BBB) and blood-brain tumour barrier (BBTB), which prevent most drugs from entering the brain and tumours. Hence, we established a novel drug delivery nanosystem of brain tumour-targeting that could self-assemble the method using an amphiphilic Zein protein isolated from corn. Zein's amphiphilicity prompted it to self-assembled into NPs, efficiently containing TMZ. This allowed us to investigate temozolomide (TMZ) for glioblastoma (GBM) treatment. To construct TMZ-encapsulated NPs (TMZ@RVG-Zein NPs), the NPs' Zein was clocked to rabies virus glycoprotein 29 (RVG29). To verify that the NPs could penetrate the BBB and precisely target and kill the GBM cancer cell line, in vitro studies were performed. The process of NPs penetrating cancer cell membranes was investigated using enzyme-linked immunosorbent assays (ELISAs) to measure the expressions of nicotinic acetylcholine receptors (nAChRs) on the U87 cell line. Therefore, effective targeted brain cancer treatment is possible by forming NP clocks, a cell-penetrating natural Zein protein with an RVG29. These NPs can penetrate the blood-brain barrier (BBB) and enter the glioblastoma (U87) cell line to release TMZ. These NPs have a distinct cocktail of biocompatibility and brain-targeting abilities, making them ideal for involving brain diseases.

摘要

胶质瘤是中枢神经系统(CNS)最主要的癌症。血脑屏障(BBB)和血脑肿瘤屏障(BBTB)的存在严重阻碍了胶质瘤治疗的效果,这两种屏障会阻止大多数药物进入大脑和肿瘤。因此,我们建立了一种新型的脑肿瘤靶向给药纳米系统,该系统可以利用从玉米中分离出的两亲性玉米醇溶蛋白自组装方法。玉米醇溶蛋白的两亲性促使其自组装成纳米颗粒(NPs),有效地包载替莫唑胺(TMZ)。这使我们能够研究替莫唑胺(TMZ)用于治疗胶质母细胞瘤(GBM)。为构建包载TMZ的纳米颗粒(TMZ@RVG - 玉米醇溶蛋白纳米颗粒),将纳米颗粒的玉米醇溶蛋白与狂犬病病毒糖蛋白29(RVG29)结合。为验证纳米颗粒能否穿透血脑屏障并精确靶向和杀死GBM癌细胞系,进行了体外研究。使用酶联免疫吸附测定(ELISA)来检测U87细胞系上烟碱型乙酰胆碱受体(nAChRs)的表达,以此研究纳米颗粒穿透癌细胞膜的过程。因此,通过形成纳米颗粒结合物,即一种带有RVG29的可穿透细胞的天然玉米醇溶蛋白,实现有效的靶向脑癌治疗是可行的。这些纳米颗粒能够穿透血脑屏障(BBB)并进入胶质母细胞瘤(U87)细胞系以释放TMZ。这些纳米颗粒具有独特的生物相容性和脑靶向能力组合,使其成为治疗脑部疾病的理想选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d8e/11002058/c8f162a9befb/gr1.jpg

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