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载有间充质干细胞的 siRNA 纳米粒药物输送系统治疗脉络膜新生血管

A drug delivery system of siRNA nanoparticles loaded by mesenchymal stem cells on choroidal neovascularization.

机构信息

Xi'an Key Laboratory of Digital Medical Technology of Ophthalmologic Imaging, Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, 710004, Shaanxi, China.

Department of Pharmaceutical Chemistry & Analysis Pharmacy, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China.

出版信息

Nanomedicine (Lond). 2024;19(26):2171-2185. doi: 10.1080/17435889.2024.2393075. Epub 2024 Sep 3.

DOI:10.1080/17435889.2024.2393075
PMID:39225143
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11485800/
Abstract

To assess mesenchymal stem cells (MSCs) as carriers for  siRNA-loaded nanoparticles (NPs) for targeted therapy of experimental choroidal neovascularization (CNV). A poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid NP was designed. The transfection efficacy of MSCs with the hybrid NPs was assessed. Mice were intravenously injected with MSCs after laser photocoagulation and CNV was assessed at 7 days post-injection. The transfection efficiency of hybrid NPs into MSCs was 72.7%. mRNA expression in 661w cells co-cultured with MSC-hybrid-siRNA NPs was significantly lower. Intravenous delivery of MSC-hybrid-siRNA NPs greatly reduced CNV area and length. Intravenous injection of MSC-hybrid-siRNA NPs achieved therapeutic efficacy in reducing CNV area. The MSC-mediated homing enabled targeted inhibition of ocular angiogenesis.

摘要

为评估间充质干细胞（MSCs）作为载体制备负载 siRNA 的纳米颗粒（NPs），用于脉络膜新生血管（CNV）的靶向治疗。设计了一种聚（乳酸-共-乙醇酸）（PLGA）-核/脂质壳杂交 NP。评估了杂交 NPs 对 MSCs 的转染效率。激光光凝后，经静脉内注射 MSCs，注射后 7 天评估 CNV。杂交 NPs 转染 MSCs 的效率为 72.7%。与 MSC-杂交-siRNA NPs 共培养的 661w 细胞中 mRNA 表达显著降低。MSC-杂交-siRNA NPs 的静脉递送大大减少了 CNV 面积和长度。静脉注射 MSC-杂交-siRNA NPs 可实现减少 CNV 面积的治疗效果。MSC 介导的归巢使眼血管生成的靶向抑制成为可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/074fea3782ab/INNM_A_2393075_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/a241a1f71704/INNM_A_2393075_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/406752b78059/INNM_A_2393075_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/008e9a41e516/INNM_A_2393075_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/389c2ecc7843/INNM_A_2393075_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/77b17cd39984/INNM_A_2393075_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/cb949e9c4445/INNM_A_2393075_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/0c218781ff8d/INNM_A_2393075_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/074fea3782ab/INNM_A_2393075_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/a241a1f71704/INNM_A_2393075_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/406752b78059/INNM_A_2393075_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/008e9a41e516/INNM_A_2393075_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/389c2ecc7843/INNM_A_2393075_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/77b17cd39984/INNM_A_2393075_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/cb949e9c4445/INNM_A_2393075_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/0c218781ff8d/INNM_A_2393075_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c959/11485800/074fea3782ab/INNM_A_2393075_F0008_C.jpg

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A drug delivery system of siRNA nanoparticles loaded by mesenchymal stem cells on choroidal neovascularization.

Nanomedicine (Lond). 2024

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[2]
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Biomed Pharmacother. 2023-11

[3]
Effect of the amount of cationic lipid used to complex siRNA on the cytotoxicity and proinflammatory activity of siRNA-solid lipid nanoparticles.

Int J Pharm X. 2023-7-3

[4]
Mesenchymal stem cells: a trojan horse to treat glioblastoma.

Invest New Drugs. 2023-4

[5]
Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing.

J Nanobiotechnology. 2023-1-16

[6]
A Trojan horse biomimetic delivery system using mesenchymal stem cells for HIF-1α siRNA-loaded nanoparticles on retinal pigment epithelial cells under hypoxia environment.

Int J Ophthalmol. 2022-11-18

[7]
PLGA-Based Composites for Various Biomedical Applications.

Int J Mol Sci. 2022-2-12

[8]
Combination of Nanomaterials in Cell-Based Drug Delivery Systems for Cancer Treatment.

Pharmaceutics. 2021-11-8

[9]
Anti-VEGF and Other Novel Therapies for Neovascular Age-Related Macular Degeneration: An Update.

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[10]
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