Products Cited in Publications Worldwide Exploiting Vitamin C as a Prooxidant to Activate Ros-Responsive Prodrugs for Potent and Selective Tumor Killing

Exploiting Vitamin C as a Prooxidant to Activate Ros-Responsive Prodrugs for Potent and Selective Tumor Killing

Peng, Xiaohua; Ali, Taufeeque; Ponnamperumage, Thilini Nimasha Fernando; Peterson, Alexis Kimberly; Li, Daniel; Gao, Hanlun; Pandey, Jatin; Rose Jakusz, Julia Anna; Fan, Heli; Koelsch, Gilbert Edward

DOI:

Abstract

Developing targeted cancer therapy with minimal side effects remains a significant challenge. Oxidative stress-based cancer therapies have gained traction in recent years. However, challenges such as limited tumor selectivity and therapeutic durability often hinder their clinical application. Here, we report a novel strategy of combining ROS-responsive prodrugs with prooxidants to achieve potent, durable, and selective tumor killing effects. This approach leverages pro-oxidants (i.e. ascorbate) to amplify oxidative stress within tumors, sensitizing cancer cells to ROS-responsive prodrugs. Both in vitro and in vivo studies confirm the anticancer synergism and selectivity of this combination therapy, which achieved complete tumor regression without recurrence, significantly outperforming single-agent treatments. This combination therapy is effective against hard-to-treat cancers like triple-negative breast cancer and glioblastoma. Our findings highlight the potential of targeting tumor redox mechanisms through a combination of ROS-responsive prodrugs and pro-oxidants, offering a promising avenue for repurposing these agents in cancer therapy.

Keywords

combination therapy ; synergistic anticancer effects ; ROS-responsive prodrugs ; triple negative breast cancer ; ROS-generating agents ; vitamin C ; complete tumor regression

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β-Lapachone

A9518154707-32-898%

β-Lapachone

284.0/100mg

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