<p>Gold nanoparticles (AuNPs) have emerged as versatile platforms for cancer diagnosis and therapy with over 3500 publications indexed annually in PubMed. Keeping in view, the present review synthesizes recent preclinical and clinical evidence (up to August 2025), covering drug and gene delivery, vaccines, diagnostics, imaging, and therapeutic applications of AuNPs. The historical background and characteristics of AuNPs are first detailed, followed by synthesis methods, including chemical, physical, and green approaches. Key considerations such as stability, drug loading efficiency, and surface modification strategies are discussed for each study, along with applications in chemotherapy, photothermal therapy, radiotherapy, sonodynamic therapy, and theranostics. AuNP-based drug delivery systems, including liposome-, polymer-, and exosome-loaded systems, enable pH- and photo-triggered release, improve cellular uptake, and provide synergistic anticancer effects. Preclinical studies demonstrated tumor-targeted delivery with extracellular vesicle-loaded AuNPs (~ 25&#xa0;nm) reducing 4T1 cell viability by ~ 50% at 0.25&#xa0;µg/µL (24&#xa0;h), while in vivo treatment suppressed tumor growth by ~ 65–70% without affecting organ histology and body weight. Macrophage- and extracellular vesicle-based AuNP systems (107&#xa0;nm) improved delivery across blood–brain barrier, achieving maximal tumor accumulation (24&#xa0;h), enhanced CD8<sup>+</sup> T-cell infiltration, with minimal systemic toxicity. Approximately ten clinical trials have investigated AuNPs, showed promise for minimally invasive tumor ablation and non-invasive detection of metastatic and solid tumors. Limitations include long-term accumulation in the liver (up to 40%&#xa0;of the injected dose) and spleen (2%&#xa0;of the injected dose), oxidative stress (kidney: 60 and Liver: 70&#xa0;nmol/g), reproductive toxicity at Doses above 10&#xa0;mg/kg, and size-dependent effects (10 and 60&#xa0;nm). Optimized surface modification, targeted delivery, and combination therapies are expected to overcome these limitations and enhance clinical translation.</p> Graphical abstract <p></p>

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Applications of Au Nanoparticles as drug delivery and theranostic nanoplatforms in cancer therapy: A comprehensive review

  • Kashif Ali Khan,
  • Bashir Ullah,
  • Zul Kamal,
  • Muhammad Esa,
  • Muhammad Riaz,
  • Muhammad Shafique,
  • Muhammad Abbas Amanat,
  • Asad Ur Rahman,
  • Anwar Ul Haq,
  • Muhammad Sarfraz,
  • Kifayat Ullah Khan,
  • Abdul Basit

摘要

Gold nanoparticles (AuNPs) have emerged as versatile platforms for cancer diagnosis and therapy with over 3500 publications indexed annually in PubMed. Keeping in view, the present review synthesizes recent preclinical and clinical evidence (up to August 2025), covering drug and gene delivery, vaccines, diagnostics, imaging, and therapeutic applications of AuNPs. The historical background and characteristics of AuNPs are first detailed, followed by synthesis methods, including chemical, physical, and green approaches. Key considerations such as stability, drug loading efficiency, and surface modification strategies are discussed for each study, along with applications in chemotherapy, photothermal therapy, radiotherapy, sonodynamic therapy, and theranostics. AuNP-based drug delivery systems, including liposome-, polymer-, and exosome-loaded systems, enable pH- and photo-triggered release, improve cellular uptake, and provide synergistic anticancer effects. Preclinical studies demonstrated tumor-targeted delivery with extracellular vesicle-loaded AuNPs (~ 25 nm) reducing 4T1 cell viability by ~ 50% at 0.25 µg/µL (24 h), while in vivo treatment suppressed tumor growth by ~ 65–70% without affecting organ histology and body weight. Macrophage- and extracellular vesicle-based AuNP systems (107 nm) improved delivery across blood–brain barrier, achieving maximal tumor accumulation (24 h), enhanced CD8+ T-cell infiltration, with minimal systemic toxicity. Approximately ten clinical trials have investigated AuNPs, showed promise for minimally invasive tumor ablation and non-invasive detection of metastatic and solid tumors. Limitations include long-term accumulation in the liver (up to 40% of the injected dose) and spleen (2% of the injected dose), oxidative stress (kidney: 60 and Liver: 70 nmol/g), reproductive toxicity at Doses above 10 mg/kg, and size-dependent effects (10 and 60 nm). Optimized surface modification, targeted delivery, and combination therapies are expected to overcome these limitations and enhance clinical translation.

Graphical abstract