Open AccessTargeted Chemoradiotherapy of Prostate Cancer Using Gold Nanoclusters with Protease Activatable Monomethyl Auristatin E
Author(s) -
Dong Luo,
Xinning Wang,
Ethan Walker,
Sarah Springer,
Ramakrishnan Gopalakrishnan,
Clemens Burda,
James P. Basilion
Publication year - 2022
Publication title -
acs applied materials and interfaces
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.535
H-Index - 228
eISSN - 1944-8252
pISSN - 1944-8244
DOI - 10.1021/acsami.1c23780
Subject(s) - radiosensitizer , prostate cancer , chemotherapy , medicine , radiation therapy , in vivo , cancer research , oncology , cancer , materials science , pharmacology , biology , microbiology and biotechnology
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.