Dietary Polyphenol-Based, Tumor Microenvironment-Responsive Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor-Targeted Therapy
5 affiliations
- 1School of Physics and Physical Engineering, Qufu Normal University, Qufu 273165, China
- 2Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100045, China
- 3Center for Nanomedicine, Key Laboratory of Green Natural Products and Pharmaceutical Intermediates in Colleges and Universities of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China
- 4Affiliated Hospital Group of Guangdong Medical University Shenzhen Baoan Central Hospital (Baoan Central Hospital of Shenzhen), Shenzhen 516003, China
- 5Key Laboratory of Bioorganic Phosphorus, Chemistry & Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China
Abstract
Cancer remains a leading global cause of morbidity and mortality. Natural polyphenols show potent antitumor activity—driven by antioxidant, anti-angiogenic, and epigenetic regulatory effects—but their clinical use is hindered by poor aqueous solubility, chemical instability in physiological conditions, low oral bioavailability, and insufficient tumor accumulation. In response, carrier-free nanomedicines, self-assembled nanostructures formed exclusively from therapeutic polyphenols without exogenous excipients or polymeric carriers, have emerged as a paradigm-shifting delivery strategy. This review provides a rigorous, mechanism-informed evaluation of how dietary polyphenol (e.g., epigallocatechin gallate [EGCG], curcumin, resveratrol, mangiferin, and quercetin)-based carrier-free smart nanoplatforms, by virtue of their tunable supramolecular architecture, enhanced stability, prolonged circulation, and passive/active tumor targeting capabilities, strategically exploit and amplify these antitumor mechanisms to confront the heterogeneity, adaptability, and therapeutic resistance inherent in malignant pathophysiology. Crucially, this review bridges translational gaps by explicitly linking molecular-level mechanistic insights to rational nanomaterial design principles and quantifiable preclinical/clinical therapeutic outcomes. Finally, it critically appraises persistent scientific, manufacturing, and regulatory challenges, including scalability, batch-to-batch reproducibility, long-term colloidal stability, in vivo fate mouthline standardized efficacy/safety assessment, and outlines forward-looking perspectives for accelerating the clinical realization of polyphenol-based carrier-free smart nanotherapeutics.
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BibTeX
@article{yang2026dietary,
title = {{Dietary Polyphenol-Based, Tumor Microenvironment-Responsive Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor-Targeted Therapy}},
author = {Liyan Yang and Xianqing Song and Zhonglei Wang},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31213895},
url = {https://www.mdpi.com/1420-3049/31/21/3895},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dietary Polyphenol-Based, Tumor Microenvironment-Responsive Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor-Targeted Therapy
AU - Liyan Yang
AU - Xianqing Song
AU - Zhonglei Wang
PY - 2026
DA - 2026/10/28
JO - Molecules
DO - 10.3390/molecules31213895
UR - https://www.mdpi.com/1420-3049/31/21/3895
AB - Cancer remains a leading global cause of morbidity and mortality. Natural polyphenols show potent antitumor activity—driven by antioxidant, anti-angiogenic, and epigenetic regulatory effects—but their clinical use is hindered by poor aqueous solubility, chemical instability in physiological conditions, low oral bioavailability, and insufficient tumor accumulation. In response, carrier-free nanomedicines, self-assembled nanostructures formed exclusively from therapeutic polyphenols without exogenous excipients or polymeric carriers, have emerged as a paradigm-shifting delivery strategy. This review provides a rigorous, mechanism-informed evaluation of how dietary polyphenol (e.g., epigallocatechin gallate [EGCG], curcumin, resveratrol, mangiferin, and quercetin)-based carrier-free smart nanoplatforms, by virtue of their tunable supramolecular architecture, enhanced stability, prolonged circulation, and passive/active tumor targeting capabilities, strategically exploit and amplify these antitumor mechanisms to confront the heterogeneity, adaptability, and therapeutic resistance inherent in malignant pathophysiology. Crucially, this review bridges translational gaps by explicitly linking molecular-level mechanistic insights to rational nanomaterial design principles and quantifiable preclinical/clinical therapeutic outcomes. Finally, it critically appraises persistent scientific, manufacturing, and regulatory challenges, including scalability, batch-to-batch reproducibility, long-term colloidal stability, in vivo fate mouthline standardized efficacy/safety assessment, and outlines forward-looking perspectives for accelerating the clinical realization of polyphenol-based carrier-free smart nanotherapeutics.
SN - 1420-3049
ER -