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适体修饰的红细胞膜包被的pH敏感纳米颗粒用于多形性胶质母细胞瘤的c-Met靶向治疗

Aptamer-Modified Erythrocyte Membrane-Coated pH-Sensitive Nanoparticles for c-Met-Targeted Therapy of Glioblastoma Multiforme.

作者信息

Liu Xianping, Chen Yixin, Geng Daoying, Li Haichun, Jiang Ting, Luo Zimiao, Wang Jianhong, Pang Zhiqing, Zhang Jun

机构信息

Department of Radiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China.

National Center for Neurological Disorders, 12 Wulumuqi Middle Road, Shanghai 200040, China.

出版信息

Membranes (Basel). 2022 Jul 29;12(8):744. doi: 10.3390/membranes12080744.

DOI:10.3390/membranes12080744
PMID:36005659
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9415068/
Abstract

Biomimetic drug delivery systems, especially red blood cell (RBC) membrane-based nanoparticle drug delivery systems (RNP), have been extensively utilized in tumor drug delivery because of their excellent biocompatibility and prolonged circulation. In this study, we developed an active targeting pH-sensitive RNP loaded with DOX by decorating an aptamer SL1 on RBC membranes (SL1-RNP-DOX) for c-Met-targeted therapy of glioblastoma multiforme (GBM). SL1 could specifically bind to c-Met, which is highly expressed in GBM U87MG cells and facilitate DOX delivery to GBM cells. In vitro studies demonstrated that U87MG cells had a higher uptake of SL1-RNP-DOX (3.25 folds) and a stronger pro-apoptosis effect than unmodified RNP-DOX. In vivo fluorescence imaging and tissue distribution further demonstrated the higher tumor distribution of SL1-RNP-DOX (2.17 folds) compared with RNP-DOX. As a result, SL1-RNP-DOX presented the best anti-GBM effect with a prolonged median survival time (23 days vs. 15.5 days) and the strongest tumor cell apoptosis in vivo among all groups. In conclusion, SL1-RNP-DOX exhibited a promising targeting delivery strategy for GBM therapy.

摘要

仿生药物递送系统，尤其是基于红细胞（RBC）膜的纳米颗粒药物递送系统（RNP），因其优异的生物相容性和延长的循环时间而被广泛应用于肿瘤药物递送。在本研究中，我们通过在红细胞膜上修饰适配体SL1（SL1-RNP-DOX），开发了一种用于多形性胶质母细胞瘤（GBM）的c-Met靶向治疗的主动靶向pH敏感RNP，其负载有阿霉素（DOX）。SL1可以特异性结合在GBM U87MG细胞中高表达的c-Met，并促进阿霉素向GBM细胞的递送。体外研究表明，U87MG细胞对SL1-RNP-DOX的摄取更高（3.25倍），并且比未修饰的RNP-DOX具有更强的促凋亡作用。体内荧光成像和组织分布进一步证明，与RNP-DOX相比，SL1-RNP-DOX的肿瘤分布更高（2.17倍）。因此，SL1-RNP-DOX在所有组中表现出最佳的抗GBM效果，中位生存时间延长（23天对15.5天），体内肿瘤细胞凋亡最强。总之，SL1-RNP-DOX为GBM治疗展示了一种有前景的靶向递送策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/23a9f2f998af/membranes-12-00744-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/9bd83415a73f/membranes-12-00744-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/b0026b2054d0/membranes-12-00744-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/126d5d9bf960/membranes-12-00744-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/9deb17798958/membranes-12-00744-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/526643bcdeff/membranes-12-00744-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/f0cff455112e/membranes-12-00744-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/fdc9455587c0/membranes-12-00744-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/23a9f2f998af/membranes-12-00744-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/9bd83415a73f/membranes-12-00744-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/b0026b2054d0/membranes-12-00744-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/126d5d9bf960/membranes-12-00744-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/9deb17798958/membranes-12-00744-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/526643bcdeff/membranes-12-00744-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/f0cff455112e/membranes-12-00744-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/fdc9455587c0/membranes-12-00744-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3280/9415068/23a9f2f998af/membranes-12-00744-g007.jpg

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[3]
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[4]
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[5]
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Bioeng Transl Med. 2023-2-14

[6]
The role of cell membrane-coated nanoparticles as a novel treatment approach in glioblastoma.

Front Mol Biosci. 2023-1-4

本文引用的文献

[1]
Quantification of Available Ligand Density on the Surface of Targeted Liposomal Nanomedicines at the Single-Particle Level.

ACS Nano. 2022-4-26

[2]
Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.

Pharmacol Res. 2021-9

[3]
A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer.

Int J Nanomedicine. 2021

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CA Cancer J Clin. 2020-6-1

[5]
Engineered superparamagnetic iron oxide nanoparticles (SPIONs) for dual-modality imaging of intracranial glioblastoma via EGFRvIII targeting.

Beilstein J Nanotechnol. 2019-9-11

[6]
Erythroliposomes: Integrated Hybrid Nanovesicles Composed of Erythrocyte Membranes and Artificial Lipid Membranes for Pore-Forming Toxin Clearance.

ACS Nano. 2019-3-19

[7]
Glioblastoma Chemoresistance: The Double Play by Microenvironment and Blood-Brain Barrier.

Int J Mol Sci. 2018-9-22

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J Neurooncol. 2017-7-6

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J Control Release. 2017-1-10

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