Development of tLyP-1 functionalized nanoliposomes with tunable internal water phase for glioma targeting.

IF 3.6 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Liposome Research Pub Date : 2023-12-01 Epub Date: 2023-03-28 DOI:10.1080/08982104.2023.2191718

Yajing Wang, Ziwei Ding, Shiqun Lv, Jie Liu, Jie Pan, Yingcong Yu, Jun Gao, Xianfeng Huang

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Abstract

tLyP-1 peptide is verified to recognize neuropilin (NRP) receptors overexpressed on the surface of both glioma cells and endothelial cells of angiogenic blood vessels. In the present study, tLyP-1 was conjugated with DSPE-PEG2000 to prepare tLyP-1-DSPE-PEG2000, which was further employed to prepare tLyP-1 functionalized nanoliposome (tLyP-1-Lip) to achieve enhancing target of glioblastoma. Process parameters were systematically studied to investigate the feasibility of tuning the internal water phase of nanoliposomes and encapsulating more Temozolomide (TMZ). The particle size, Zeta potential, and encapsulation efficiency of tLyP-1-Lip/TMZ were fully characterized in comparison with conventional nanoliposomes (Lip-TMZ) and PEGylated nanoliposomes (PEG-Lip/TMZ). The release behaviors of TMZ from PEG-Lip/TMZ and tLyP-1-Lip/TMZ are similar and slower than TMZ-Lip in acidic solutions. The tLyP-1-Lip/TMZ demonstrated the strongest cytotoxicity in comparison with TMZ-Lip and PEG-Lip/TMZ in both U87 and HT22 cells, and displayed the highest cellular internalization. The pharmacokinetic studies in rats revealed that tLyP-1-Lip/TMZ showed a 1.4-fold (p < 0.001) increase in AUC_{INF_obs} and a 1.4-fold decrease (p < 0.01) in clearance compared with PEG-Lip/TMZ. We finally confirmed by in vivo imaging that tLyP-1-Lip were able to penetrate the brains and tumors of mice.

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用于胶质瘤靶向的具有可调内部水相的tLyP-1功能化纳米脂质体的开发。

经证实，tLyP-1肽可识别胶质瘤细胞和血管内皮细胞表面过表达的神经匹林(neuropilin, NRP)受体。本研究将tLyP-1与DSPE-PEG2000偶联制备tLyP-1-DSPE-PEG2000，并进一步制备tLyP-1功能化纳米脂质体(tLyP-1- lip)，以达到对胶质母细胞瘤的增强目的。系统地研究了工艺参数，探讨了调节纳米脂质体内水相和包封更多替莫唑胺(TMZ)的可行性。通过与常规纳米脂质体(Lip-TMZ)和聚乙二醇化纳米脂质体(PEG-Lip/TMZ)的比较，对tLyP-1-Lip/TMZ的粒径、Zeta电位和包封效率进行了全面表征。在酸性溶液中，PEG-Lip/TMZ和tLyP-1-Lip/TMZ的释放行为与TMZ- lip相似，且释放速度较TMZ- lip慢。与TMZ- lip和PEG-Lip/TMZ相比，tLyP-1-Lip/TMZ在U87和HT22细胞中均表现出最强的细胞毒性，并表现出最高的细胞内化。大鼠药代动力学研究显示，与PEG-Lip/TMZ相比，tLyP-1-Lip/TMZ的AUCINF_obs增加1.4倍(p 0.001)，清除率降低1.4倍(p 0.01)。我们最终通过体内成像证实了tLyP-1-Lip能够穿透小鼠的大脑和肿瘤。

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来源期刊

Journal of Liposome Research 生物-生化与分子生物学

CiteScore

10.50

自引率

2.30%

发文量

审稿时长

3 months

期刊介绍： The Journal of Liposome Research aims to publish original, high-quality, peer-reviewed research on the topic of liposomes and related systems, lipid-based delivery systems, lipid biology, and both synthetic and physical lipid chemistry. Reviews and commentaries or editorials are generally solicited and are editorially reviewed. The Journal also publishes abstracts and conference proceedings including those from the International Liposome Society. The scope of the Journal includes: Formulation and characterisation of systems Formulation engineering of systems Synthetic and physical lipid chemistry Lipid Biology Biomembranes Vaccines Emerging technologies and systems related to liposomes and vesicle type systems Developmental methodologies and new analytical techniques pertaining to the general area Pharmacokinetics, pharmacodynamics and biodistribution of systems Clinical applications. The Journal also publishes Special Issues focusing on particular topics and themes within the general scope of the Journal.