Targeted intracellular glucose oxidase nanotherapy enables single-dose treatment of prostate cancer.

Glucose oxidase (GOX) is an enzyme that generates hydrogen peroxide (H2O2) and is considered a potential cancer therapy. However, effective delivery of GOX to tumor cells remains challenging, and parenteral administration leads to systemic toxicity and immunogenicity. In this study, GOX is encapsulated within a poly-l-lysine-grafted-polyethylene glycol (PLL-g-PEG) copolymer to enhance tumor-localized cytotoxicity and reduce systemic toxicity. A monoclonal antibody targeting the prostate-specific membrane antigen (PSMA) is conjugated to the nano-polymeric shell to enable receptor-mediated tumor targeting. The nanoparticles (NPs), with an average diameter of 30 nm and a neutral ζ-potential, have higher cytotoxicity against PSMA-expressing prostate cancer cells in vitro than free GOX. Next, single-dose therapeutic efficacy via the intratumoral route is evaluated in vivo using murine prostate tumor models. The intratumorally injected targeted NPs effectively suppress tumor growth and prolong survival by 4-fold compared with untreated mice and by 1.8-fold compared with free GOX. In vivo biocompatibility experiments indicate that the NPs exhibit a significant reduction in GOX's general toxicity and do not elicit an adverse immune response. Together, these results establish encapsulation and targeted delivery of GOX as a means to provide an efficient and safer therapeutic agent for the treatment of prostate cancer.