Pharmacological ascorbate potentiates combination nanomedicines and reduces cancer cell stemness to prevent post-surgery recurrence and systemic metastasis

Conventional chemotherapy targets proliferative cancer cells to halt tumor progression or regress tumors. However, the plasticity of tumor cells enables their phenotypical changes to acquire chemo-resistance, leading to treatment failure or tumor recurrence after a successful treatment course. Here, we report the use of high-dose pharmacologic ascorbate to potentiate treatment efficacy of nanoscale coordination polymers (NCPs) delivering two clinical combinations of chemotherapeutics, carboplatin/docetaxel and oxaliplatin/SN38, and to target metabolic plasticity of tumor cells. Combination treatments of high-dose ascorbate and NCPs overcome multidrug resistance by significantly reducing the abundance of cancer stem cells (CSCs) in solid tumors, as evidenced by reduced expression of tumor pluripotency factors. The clearance of CSCs inhibits post-surgery recurrence and systemic metastasis in multiple mouse models of cancer.

Automated summary

Conventional chemotherapy alone may fail due to the plasticity of tumor cells acquiring chemo-resistance. This study demonstrates that high-dose pharmacologic ascorbate, in combination with nanoscale coordination polymers (NCPs) delivering chemotherapeutics, can effectively reduce cancer stem cells (CSCs) in solid tumors and inhibit tumor recurrence and metastasis in mouse models of cancer.