Immunomodulatory green nanomedicine production, tumor cellular targeting, in vivo biodistributions and preclinical therapeutic efficacy investigations of resveratrolfunctionalized gold and theranostic 198gold nanoparticles

Abstract

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. In vivo 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 dualfunctional 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 in vivo 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 tumortargeting agent in oncology, particularly for the application of RESV–198AuNP in cancer treatments.