Gold Nanoparticle-Enabled Cancer Therapy: Translational Design Rules for Photothermal–Immunotherapy and Multimodal Precision Oncology

Gold nanoparticles (AuNPs) are versatile cancer-therapy platforms with tunable plasmonic properties, high atomic number, accessible surface chemistry, and potential for integration into theranostic systems. By controlling size, morphology, surface composition, and cargo-loading strategies, AuNPs can support photothermal therapy (PTT), chemotherapy delivery, nucleic-acid transport, radiosensitization, photodynamic therapy (PDT), sonodynamic therapy (SDT), and image-guided treatment. Among these applications, AuNP-mediated PTT is particularly attractive because localized hyperthermia can induce tumor-cell injury, support controlled cargo release, and, under appropriate conditions, contribute to immunogenic cell death and remodeling of the tumor immune microenvironment. However, promising preclinical findings have not translated into widespread routine oncology practice. Major barriers include heterogeneous tumor accumulation, limited penetration beyond perivascular regions, mononuclear phagocyte system uptake, uncertain long-term biodistribution and clearance, inadequate manufacturing reproducibility, and incomplete safety standardization. The enhanced permeability and retention effect is variable across tumors, lesions, and patients; it should not be regarded as a universal basis for clinical nanoparticle delivery. This review summarizes the physicochemical design principles governing AuNP biological performance and critically evaluates their major therapeutic uses in oncology. Particular emphasis is placed on photothermal–immunotherapy, tumor-microenvironment modulation, multimodal synergy, and pharmacokinetic, toxicological, manufacturing, and regulatory barriers. We propose a translational framework connecting material quality attributes, route of administration and in vivo fate, local energy delivery and thermal dosimetry, immune activation, patient selection, and clinically meaningful endpoints. This framework may guide development of more reproducible, controllable, and clinically relevant AuNP cancer therapies.