Tumor-Selective Cascade-Amplified Dual-Prodrugs Activation for Synergistic Oxidation-Chemotherapy

Abstract

Efficacy of prodrugs in cancer therapy requires selective and efficient drug activation in cancer cells.Here, we report a novel dual-prodrug delivery system with tumor-selective cascade amplified prodrug activation for synergistic oxidation-chemotherapy. Cancer cells overexpressed cathepsin B (CTB)activatable near-infrared (NIR) hemicyanine prodrug (CyNH-Citval) were encapsulated by reactive oxygen species (ROS)-responsive polyprodrug of doxorubicin (DOX) (PTK DOX ) to obtain PTK DOX/Cy .Upon uptake of PTK DOX/Cy by cancer cells, prodrug CyNH-Citval was activated with NIR fluorescence turn-on, restored toxicity to dysfunction of mitochondria with elevated intracellular ROS levels, which subsequently activated the polyprodrug PTK DOX , thereby causing activation of cascade and amplified DOX. Overall, these results indicate that enzyme-mediated initiation of drug activation and amplification of cascade ROS ultimately causes selective and efficient prodrug activation in tumors with synergistic oxidation and chemotherapy. These findings provide new insights to inform precise cooperative cancer therapy.

Responsive calcium-derived nanoassemblies induce mitochondrial disorder to promote tumor calcification

“…Inducing micro/nano-material alterations in tumors was gradually becoming an unconventional but promising approach for the treatment of malignant tumors. [36][37][38][39][40][41] In recent years, researchers have begun to investigate calcium-based nanomaterials such as calcium peroxide (CaO 2 ) 42 and calcium carbonate (CaCO 3 ), 9 as TME-responsive materials for tumor therapeutic effects, and have explored the action mechanism of Ca 2+ . We here choose CaHPO 4 , which could be controllable to synthesize and has been widely used in supplements.…”

Design, synthesis and anticancer evaluation of imamine-1,3,5-triazine derivatives

“…4,5 For example, chemotherapy is the mainstay of clinical treatment for cancer, but its application is still limited due to poor selectivity and serious side effects. 6 In addition, more than 90% of deaths in cancer patients receiving conventional chemotherapy are due to multidrug resistance. 7 Therefore, the development of efficacious, novel and less cytotoxic anticancer agents is imperative for cancer treatment.…”

Fine-tuning the sequential drug release of nano-formulated mutual prodrugs dictates the combination effects

“…Nanotechnology has enabled the systemic delivery of multiple drugs with various properties to maximize the efficacy of combination therapies. [7][8][9] For example, Vyxeos, a liposomal formulation co-loaded with cytarabine and daunorubicin at a xed ratio of 5 : 1, enables co-delivery of both drugs to kill cancer cells; in a phase III clinical trial among patients with acute myeloid leukemia, Vyxeos extended patient survival by 6-10 months compared to standard treatments. 10 However, formulations such as this one focus mainly the co-loading of the a Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300071, China.…”