Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

Zhang, Bo; Hu, Yu; Pang, Zhiqing

doi:10.3389/fphar.2017.00952

Cited by 152Nanoparticle-Based Drug DeliveryNanoplatforms for cancer theranosticsDrug Transport and Resistance Mechanisms

Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

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Zhang, Bo, Hu, Yu, Pang, Zhiqing·2017·Frontiers in Pharmacology

DOI 10.3389/fphar.2017.00952PMC PMC5744178

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Abstract

Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents.

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Likely molecular targets in ECM include ECM proteins (collagen, fibronectin), proteoglycan, growth factor receptors, and transmembrane receptors.
“The likely molecular targets in ECM include ECM proteins (collagen, fibronectin), proteoglycan, growth factor receptors, and transmembrane receptors [44].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [44]
The ECM section (page unavailable) identifies proteoglycans and fibrous proteins, including collagen and fibronectin, as ECM components. The section on improving interstitial transport discusses blocking growth-factor signaling and acting on the Smoothened receptor to reduce ECM production, but it does not identify growth-factor or transmembrane receptors as molecular targets in the ECM. (LLM, conf=0.85)
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Authors: Zhang, B., Hu, Y., & Pang, Z.
Affiliations: Fudan University (CN)
Wuhan Union Hospital (CN)
Corresponding author: Hu, Yu
Pang, Zhiqing
ORCID: Zhang, Bo
Hu, Yu
Pang, Zhiqing
Venue: Frontiers in Pharmacology
Publisher: Frontiers Media SA
Published: 2017-12-22
Volume: 8
Pages: 952-952
ISSN: 1663-9812 (ISSN-L)
DOI: 10.3389/fphar.2017.00952
PMC: PMC5744178
OpenAlex: W2776171184
Cited by: 152
References: 173
Citations by year: 2026: 17 · 2025: 11 · 2024: 12 · 2023: 17 · 2022: 18 · 2021: 21 · 2020: 30 · 2019: 18 · 2018: 8
FWCI: 1.11
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Pharmacology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: National Natural Science Foundation of China (81361140344, 81773283, 81600175, 81472757)
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords: tumor microenvironment modulation, nanomedicine delivery, enhanced permeability and retention effect, tumor perfusion, interstitial transport, interstitial fluid pressure, extracellular matrix, stromal cells, blood flow heterogeneity, liposomes, micelles, nanoparticles, active targeting, combination chemotherapy

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Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

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