Immunomodulatory green nanomedicine production, tumor cellular targeting, <i>in vivo</i> biodistributions and preclinical therapeutic efficacy investigations of resveratrol-functionalized gold and theranostic ¹⁹⁸gold nanoparticles

Prostate cancer remains a major global health concern demanding innovative therapeutic strategies. This study introduces a novel green nanotechnology approach for the development of a nanomedicine agent, also referred to as a nano-radiopharmaceutical, which integrates the antitumor and high antioxidant capacity of resveratrol phytochemical (RESV) with radioactive gold nanoparticles (¹⁹⁸AuNPs) for targeted prostate cancer therapy and diagnostics. The radioactive formulation, RESV-¹⁹⁸AuNP, was developed at the University of Missouri Research Reactor (MURR) using neutron-activated gold-198, which exhibited high radionuclidic and radiochemical purity. Stability testing in rat serum and saline demonstrated durability of up to 15 days. <i>In vivo</i> biodistribution studies in CF-1 mice and PC-3 tumor-bearing SCID mice have provided insights into pharmacokinetics and optimum tumor retention. Intratumoral administration of RESV-¹⁹⁸AuNP in SCID mice demonstrated strong retention within prostate cancer xenografts, suggesting tumor-specific uptake and retention. This study underscores the potential of RESV-¹⁹⁸AuNP as a dual-functional nano-radiopharmaceutical for prostate cancer theranostics. By combining resveratrol's anticancer properties with the therapeutic and imaging benefits of ¹⁹⁸AuNPs, this platform offers a promising avenue for improving treatment efficacy and enabling real-time therapeutic response monitoring. This research reveals the potential of RESV as a tumor-targeting agent and introduces a new perspective of green nanotechnology for dual anti-inflammatory radiosynovectomy as well as for use in cancer treatment. In-depth <i>in vivo</i> studies on the therapeutic efficacy of intratumorally administered RESV-¹⁹⁸AuNP revealed that over 85% of the injected dose (ID) remained within prostate tumors for up to 24 h. By the fourth week post-treatment, the treated group exhibited a greater than tenfold reduction in tumor volumes than the control group receiving saline. This study highlights emerging opportunities in green nanotechnology and introduces a clinically feasible approach to utilize resveratrol as a tumor-targeting agent in oncology, particularly for the application of RESV-¹⁹⁸AuNP in cancer treatments.