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麝香酮修饰的“导向”增强了乳铁蛋白修饰的多西他赛脂质体的脑靶向疗效和抗胶质瘤作用。

"Guide" of muscone modification enhanced brain-targeting efficacy and anti-glioma effect of lactoferrin modified DTX liposomes.

作者信息

Qi Na, Duan Wenjuan, Gao Duan, Ma Ningzhu, Zhang Jianguo, Feng Jianfang, Li Aimin

机构信息

Cancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou China.

Department of Pharmacy Guilin Medical University Guilin China.

出版信息

Bioeng Transl Med. 2022 Aug 18;8(2):e10393. doi: 10.1002/btm2.10393. eCollection 2023 Mar.

DOI:10.1002/btm2.10393
PMID:36925685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10013770/
Abstract

Glioma is one of the most aggressive malignant diseases for human health. It is difficult to resect completely due to their invasiveness. The targeted delivery, as a noninvasive approach, is a major strategy for the development of treatments for brain tumors. Lactoferrin (Lf) receptors are over-expressed in both brain endothelial cells and glioma cells. Macromolecular Lf modified nanoparticles have been shown to enhance the brain targeting. Muscone is a "guide" drug that have been demonstrated to promote liposomes into the brain by modification. To further enhance the brain-targeting efficacy of Lf modified carriers, we designed that Lf and muscone dual-modified liposomes cross blood-brain barrier (BBB) and target to brain for enhanced docetaxel (DTX) brain delivery. The results showed that we successfully prepared Lf and muscone dual-modified liposomes (Lf-LP-Mu-DTX), the number of Lf molecules connected to the surface of per liposome was 28. Lf-LP-Mu-DTX increased uptake in both U87-MG cells and hCMEC/D3 cells, enhanced penetration of U87-MG tumor spheroid and in vitro BBB model, had better in vitro and in vivo anti-tumor effects. In conclusion, "guide" of muscone modification enhanced brain-targeting efficacy of Lf modified liposomes, Lf and muscone dual-modified docetaxel loaded liposomes present a potential brain-targeting drug delivery system for use in the future treatment of gliomas.

摘要

胶质瘤是对人类健康最具侵袭性的恶性疾病之一。由于其侵袭性，很难完全切除。靶向递送作为一种非侵入性方法，是脑肿瘤治疗发展的主要策略。乳铁蛋白（Lf）受体在脑内皮细胞和胶质瘤细胞中均过度表达。已证明大分子Lf修饰的纳米颗粒可增强脑靶向性。麝香酮是一种“导向”药物，已证明通过修饰可促进脂质体进入大脑。为了进一步提高Lf修饰载体的脑靶向疗效，我们设计了Lf和麝香酮双修饰脂质体穿过血脑屏障（BBB）并靶向大脑以增强多西他赛（DTX）的脑递送。结果表明，我们成功制备了Lf和麝香酮双修饰脂质体（Lf-LP-Mu-DTX），每个脂质体表面连接的Lf分子数为28个。Lf-LP-Mu-DTX增加了U87-MG细胞和hCMEC/D3细胞的摄取，增强了U87-MG肿瘤球体和体外血脑屏障模型的穿透能力，具有更好的体外和体内抗肿瘤效果。总之，麝香酮修饰的“导向”增强了Lf修饰脂质体的脑靶向疗效，Lf和麝香酮双修饰的载多西他赛脂质体为未来胶质瘤治疗提供了一种潜在的脑靶向给药系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/7067ecb9a7a2/BTM2-8-e10393-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/9fa2a93c6530/BTM2-8-e10393-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/3cda4f26f2fa/BTM2-8-e10393-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/4cdb47ea0985/BTM2-8-e10393-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/2f6340386004/BTM2-8-e10393-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/9bf761517b21/BTM2-8-e10393-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/6553b45ee16c/BTM2-8-e10393-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/f432774bad0d/BTM2-8-e10393-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/6a50ffaf5366/BTM2-8-e10393-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/7067ecb9a7a2/BTM2-8-e10393-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/9fa2a93c6530/BTM2-8-e10393-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/3cda4f26f2fa/BTM2-8-e10393-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/4cdb47ea0985/BTM2-8-e10393-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/2f6340386004/BTM2-8-e10393-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/9bf761517b21/BTM2-8-e10393-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/6553b45ee16c/BTM2-8-e10393-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/f432774bad0d/BTM2-8-e10393-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/6a50ffaf5366/BTM2-8-e10393-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/10013770/7067ecb9a7a2/BTM2-8-e10393-g004.jpg

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