Overcoming the biological barriers in the tumor microenvironment for improving drug delivery and efficacy
Abstract
The delivery of drugs to tumors by nanoparticles is a rapidly growing field. However, the complex tumor microenvironment (TME) barriers greatly hinder drug delivery to tumors. In this study, we first summarized the barriers in TME, including anomalous vasculature, rigid extracellular matrix, hypoxia, acidic pH, irregular enzyme level, altered metabolism pathway and immunosuppressive conditions. To overcome these barriers, many strategies have been developed, such as modulating TME, active targeting by ligand modification and biomimetic strategies, and TME-responsive drug delivery strategies to improve nanoparticle penetration, cellular uptake and drug release. Although extensive progress has been achieved, there are still many challenges, which are discussed in the last section. Overall, we carefully discuss the landscape of TME, development for improving drug delivery, and challenges that need to be further addressed.
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Tumor penetration is hindered by a dense extracellular matrix, elevated interstitial pressure, and abnormal vasculature.
“Tumor penetration is hindered by a dense extracellular matrix, elevated interstitial pressure, and abnormal vasculature [143–145]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [145]
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Phage therapy in oncology: opportunities for cancer prevention and treatment
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- Authors
- Zhou, Y., Chen, X., Cao, J., & Gao, H.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- Cao, Jun
- Gao, Huile
- Venue
- Journal of Materials Chemistry B
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2020
- Volume
- 8
- Issue
- 31
- Pages
- 6765-6781
- ISSN
- 2050-750X (ISSN-L)
- 2050-7518
- OpenAlex
- W3014250283
- Cited by
- 213
- References
- 15
- Citations by year
- 2026: 40 · 2025: 37 · 2024: 21 · 2023: 35 · 2022: 34 · 2021: 25 · 2020: 21
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Materials Chemistry B (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Higher Education Discipline Innovation Project (B18035)
- National Natural Science Foundation of China (81961138009)
- Department of Science and Technology of Sichuan Province (19YYJC2250)
- Fundamental Research Funds for the Central Universities
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- tumor microenvironment, nanoparticle drug delivery, extracellular matrix stiffness, tumor hypoxia, low pH, cancer metabolism, immunosuppression, ligand-modified nanoparticles, biomimetic nanoparticles, nanoparticle penetration, cellular uptake, drug release
- MeSH terms
- Tumor Hypoxia, Animals, Extracellular Matrix, Humans, Hydrogen-Ion Concentration, Drug Delivery Systems, Tumor Microenvironment
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