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MMP-13 酶和 pH 响应治疗性纳米平台治疗骨关节炎。

MMP-13 enzyme and pH responsive theranostic nanoplatform for osteoarthritis.

机构信息

Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.

Research Centre for Regenerative Medicine, Department of Orthopedics, The First Affiliated Hospital of Gaungxi Medical University, Nanning, 530021, China.

出版信息

J Nanobiotechnology. 2020 Aug 27;18(1):117. doi: 10.1186/s12951-020-00666-7.

DOI:10.1186/s12951-020-00666-7
PMID:32854712
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7450974/
Abstract

Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA), which enables the development of stimulus-responsive drug delivery system with high specificity for OA. We herein demonstrate a nano-micelle based stimuli-responsive theranostic strategy with reporting and drug release controlled by acidic pH and MMP-13 for OA therapy. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an anti-inflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro and vivo evidences.

摘要

刺激响应性治疗仅在感兴趣的病变部位精确控制治疗效果，这使其成为诊断和成像引导的精准治疗的有前途的方法。酸性环境和过表达的基质金属蛋白酶-13（MMP-13）是骨关节炎（OA）的典型标志物，这使得具有针对 OA 高度特异性的刺激响应性药物递送系统的发展成为可能。我们在此展示了一种基于纳米胶束的刺激响应性治疗策略，该策略通过酸性 pH 和 MMP-13 控制报告和药物释放，用于 OA 治疗。该纳米平台结合了一种专门针对软骨的基序、一种响应基质金属蛋白酶-13 的基序，以专门报告 OA 状况和纳米胶束的生物动力学，一种来自中药的抗炎药物（如补骨脂素（PSO）），以及一种生物相容性聚合物骨架，以响应酸性 OA 条件持续释放药物。通过体外和体内证据全面证明了这种靶向精准治疗的高效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/432b6627a7ad/12951_2020_666_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/e6d3fd493818/12951_2020_666_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/e1a4cfab5559/12951_2020_666_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/f6f36d2711cb/12951_2020_666_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/e241b4c3b01b/12951_2020_666_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/368881235021/12951_2020_666_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/3466daffa6c9/12951_2020_666_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/407f199b8620/12951_2020_666_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/432b6627a7ad/12951_2020_666_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/e6d3fd493818/12951_2020_666_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/e1a4cfab5559/12951_2020_666_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/f6f36d2711cb/12951_2020_666_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/e241b4c3b01b/12951_2020_666_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/368881235021/12951_2020_666_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/3466daffa6c9/12951_2020_666_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/407f199b8620/12951_2020_666_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88c/7450974/432b6627a7ad/12951_2020_666_Fig8_HTML.jpg

相似文献

[1]
MMP-13 enzyme and pH responsive theranostic nanoplatform for osteoarthritis.

J Nanobiotechnology. 2020-8-27

[2]
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[3]
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[4]
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[5]
The NAD-Dependent Deacetylase Sirtuin-1 Regulates the Expression of Osteogenic Transcriptional Activator Runt-Related Transcription Factor 2 (Runx2) and Production of Matrix Metalloproteinase (MMP)-13 in Chondrocytes in Osteoarthritis.

Int J Mol Sci. 2016-6-28

[6]
Effects of FGF-2 and FGF receptor antagonists on MMP enzymes, aggrecan, and type II collagen in primary human OA chondrocytes.

Scand J Rheumatol. 2015

[7]
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[8]
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[9]
The Involvement of Mutual Inhibition of ERK and mTOR in PLCγ1-Mediated MMP-13 Expression in Human Osteoarthritis Chondrocytes.

Int J Mol Sci. 2015-8-4

[10]
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Theranostics. 2019-1-1

引用本文的文献

[1]
Recent advances in injectable hydrogels for osteoarthritis treatments.

Front Bioeng Biotechnol. 2025-8-6

[2]
Targeted therapy for knee osteoarthritis: From basic to clinics.

Medicine (Baltimore). 2025-8-15

[3]
Nanomedicine for chronic pain management: From pathophysiology to engineered drug delivery systems.

Mater Today Bio. 2025-6-10

[4]
A review of nanomaterials in osteoarthritis treatment and immune modulation.

Regen Biomater. 2025-6-4

[5]
A versatile platform based on matrix metalloproteinase-sensitive peptides for novel diagnostic and therapeutic strategies in arthritis.

Bioact Mater. 2025-1-18

[6]
The Role of Nanoparticles in Accelerating Tissue Recovery and Inflammation Control in Physiotherapy Practices.

Cureus. 2024-11-12

[7]
Edge advances in nanodrug therapies for osteoarthritis treatment.

Front Pharmacol. 2024-10-30

[8]
Controlled Stimulus-Responsive Delivery Systems for Osteoarthritis Treatment.

Int J Mol Sci. 2024-11-2

[9]
Therapeutic Controlled Release Strategies for Human Osteoarthritis.

Adv Healthc Mater. 2025-1

[10]
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本文引用的文献

[1]
Mechanisms explaining the efficacy of psoralidin in cancer and osteoporosis, a review.

Pharmacol Res. 2019-6-28

[2]
Cartilage-targeting dexamethasone prodrugs increase the efficacy of dexamethasone.

J Control Release. 2018-12-17

[3]
Dual-functional lipid polymeric hybrid pH-responsive nanoparticles decorated with cell penetrating peptide and folate for therapy against rheumatoid arthritis.

Eur J Pharm Biopharm. 2018-6-19

[4]
Chondrocyte affinity peptide modified PAMAM conjugate as a nanoplatform for targeting and retention in cartilage.

Nanomedicine (Lond). 2018-3-12

[5]
Synthetic Polymeric Mixed Micelles Targeting Lymph Nodes Trigger Enhanced Cellular and Humoral Immune Responses.

ACS Appl Mater Interfaces. 2018-1-10

[6]
Protective effects of psoralidin on IL‑1β‑induced chondrocyte apoptosis.

Mol Med Rep. 2017-12-11

[7]
Nitric Oxide Nanosensors for Predicting the Development of Osteoarthritis in Rat Model.

ACS Appl Mater Interfaces. 2017-7-20

[8]
Cryptotanshinone protects against IL-1β-induced inflammation in human osteoarthritis chondrocytes and ameliorates the progression of osteoarthritis in mice.

Int Immunopharmacol. 2017-6-27

[9]
Mechanisms of pH-Sensitivity and Cellular Internalization of PEOz-b-PLA Micelles with Varied Hydrophilic/Hydrophobic Ratios and Intracellular Trafficking Routes and Fate of the Copolymer.

ACS Appl Mater Interfaces. 2017-2-17

[10]
Achyranthes bidentate saponins protect rat articular chondrocytes against interleukin-1β-induced inflammation and apoptosis in vitro.

Kaohsiung J Med Sci. 2017-2

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