Targeting tumor extracellular matrix with nanoparticles to circumvent therapeutic resistance
Abstract
Each stage of tumor development is intrinsically linked to the tumor microenvironment (TME), wherein the extracellular matrix (ECM) serves as a vital and abundant component in tumor tissues. The ECM is a non-cellular, three-dimensional macromolecular network scaffold that provides structural support to cells, stores bioactive molecules, and mediates signaling pathways through specific binding to cell surface receptors. Moreover, the ECM in tumor tissues plays a crucial role in impeding drug diffusion and resisting apoptosis induced by conventional anti-cancer therapies that primarily target cancer cells. Therefore, directing attentions towards the tumor ECM can facilitate the identification of novel targets and the development of new therapies. This review aims to summarize the composition, structure, remodeling, and function of tumor ECM, its association with drug resistance, and current targeting strategies, with a specific emphasis on nanoparticles (NPs).
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A hardened extracellular matrix network considerably restricts the penetration of therapeutic drugs, ultimately affecting their efficacy.
“Studies have demonstrated that the hardened ECM network considerably restricts the penetration of therapeutic drugs, ultimately affecting their efficacy (36).”
From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [36]
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- Authors
- Ding, X., Liang, Y., Zhou, S., Wu, Y., Sałata, P., Mikolajczk-Martinez, A., Khosrawipour, V., & Zhang, Z.
- Affiliations
- Fudan University (CN)
- Wrocław University of Environmental and Life Sciences (PL)
- Corresponding author
- Khosrawipour, Veria
- Zhang, Zhiwen
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2025-07
- Volume
- 383
- Pages
- 113786
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W4409885575
- Cited by
- 20
- References
- 279
- Citations by year
- 2026: 15 · 2025: 5
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of the People's Republic of China
- National Key Research and Development Program of China (2023YFE0104300)
- National Natural Science Foundation of China (32271461)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- tumor extracellular matrix, nanoparticles, drug resistance, tumor microenvironment, extracellular matrix remodeling, apoptosis resistance, cancer therapy
- MeSH terms
- Animals, Antineoplastic Agents, Extracellular Matrix, Humans, Neoplasms, Drug Delivery Systems, Drug Resistance, Neoplasm, Nanoparticles, Tumor Microenvironment
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