{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "School of Physics and Physical Engineering, Qufu Normal University, Qufu 273165, China",
    "Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100045, China",
    "Center 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",
    "Affiliated Hospital Group of Guangdong Medical University Shenzhen Baoan Central Hospital (Baoan Central Hospital of Shenzhen), Shenzhen 516003, China",
    "Key Laboratory of Bioorganic Phosphorus, Chemistry & Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Liyan Yang",
      "orcid": "0000-0001-5026-2808"
    },
    {
      "affs": [
        3
      ],
      "name": "Xianqing Song"
    },
    {
      "affs": [
        0,
        2,
        4
      ],
      "name": "Zhonglei Wang",
      "orcid": "0000-0002-3185-0257"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5fvxn5j64rd7x.bib",
  "cited_by": 0,
  "doi": "10.3390/molecules31213895",
  "fulltext_url": null,
  "id": "5fvxn5j64rd7x",
  "issns": [
    "1420-3049"
  ],
  "landing_url": "https://www.mdpi.com/1420-3049/31/21/3895",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2502|Nanoparticle-Based Drug Delivery"
    ]
  ],
  "openalex": "W7224086158",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/5fvxn5j64rd7x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:42Z",
      "native_id": "10.3390/molecules31213895",
      "source": "crossref",
      "url": "https://www.mdpi.com/1420-3049/31/21/3895"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2502|Nanoparticle-Based Drug Delivery",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Dietary Polyphenol-Based, Tumor Microenvironment-Responsive Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor-Targeted Therapy",
  "title_text": "Dietary Polyphenol-Based, Tumor Microenvironment-Responsive Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor-Targeted Therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:42Z",
  "url": "https://research.draconitic.com/paper/5fvxn5j64rd7x",
  "venue": "Molecules",
  "versions": []
}