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Targeted Chemoradiotherapy of Prostate Cancer Using Gold Nanoclusters with Protease Activatable Monomethyl Auristatin E.

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Combined radiotherapy (RT) and chemotherapy are prescribed to patients with advanced prostate cancer (PCa) to increase their survival; however, radiation-related side effects and systematic toxicity caused by chemotherapeutic drugs are… Click to show full abstract

Combined radiotherapy (RT) and chemotherapy are prescribed to patients with advanced prostate cancer (PCa) to increase their survival; however, radiation-related side effects and systematic toxicity caused by chemotherapeutic drugs are unavoidable. To improve the precision and efficacy of concurrent RT and chemotherapy, we have developed a PCa-targeted gold nanocluster radiosensitizer conjugated with a highly potent cytotoxin, monomethyl auristatin E, PSMA-AuNC-MMAE, for RT and chemotherapy of PCa. This approach resulted in enhanced uptake of NCs by PSMA-positive cancer cells, targeted chemotherapy, and increased efficacy of RT both in vitro and in vivo. In addition, the combination of gold and MMAE further increased the efficacy of either of the agents delivered alone or simultaneously but not covalently linked. The PSMA-AuNC-MMAE conjugates improve the specificity and efficacy of radiation and chemotherapy, potentially reducing the toxicity of each therapy and making this an attractive avenue for clinical treatment of advanced PCa.

Keywords: cancer; chemotherapy; gold; monomethyl auristatin; efficacy; prostate cancer

Journal Title: ACS applied materials & interfaces
Year Published: 2022

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