A reactive oxygen species-replenishing coordination polymer nanomedicine disrupts redox homeostasis and induces concurrent apoptosis-ferroptosis for combinational cancer therapy

An antioxidant and antibacterial polydopamine-modified thermo-sensitive hydrogel dressing for Staphylococcus aureus-infected wound healing

“…The intracellular ROS level was upregulated by exogeneous H 2 O 2 and monitored using a 2′,7′-dichlorofluorescein diacetate (DCFH-DA) probe. 59,60 The fluorescence intensity of the PDA/P2–4 group was the lowest, similar to that of the control group, while the fluorescence intensity of the P2 group was similar to that of the H 2 O 2 group (Fig. S14†).…”

Reactive oxygen species-upregulating nanomedicines towards enhanced cancer therapy

“…In addition to enzymes that catalyze the production of H 2 O 2 , some anticancer drugs, such as camptothecin (CPT) 42,43 and doxorubicin (DOX), 44,45 and biological molecules including β-lapachone (Lapa) 46–48 and cinnamaldehyde (CA) 49,50 are capable of elevating intracellular ROS levels. DOX induces the upregulation of ROS through the activation of NADPH NOXs in the mitochondria, 51 while Lapa catalyzes the generation of H 2 O 2 in situ mainly through the catalysis of NAD(P)H:quinone oxidoreductase-1 (NQO1), which is overexpressed in many types of cancer. 52 In addition, CA induces the depletion of intracellular thiols to cause an imbalance in the redox state and ROS elevation.…”

“…Besides Lapa, other biological molecules (such cinnamaldehyde) have been utilized to enable ROS-enhanced CT. 51,213 Various drug carriers with ROS-sensitive moieties, such as thioketal (TK), boronic ester, and alkylene sulfide, have been developed to co-deliver these ROS-generating molecules and chemotherapeutic agents for ROS upregulation-activated, tumor-specific chemotherapy. 214,215 We developed an ROS-responsive and ROS-regenerative system based on CA-embedded polymer NPs, where CA was released upon thioacetal breakdown in response to ROS for ROS regeneration.…”

“…As mentioned above, elevating the tumoral H 2 O 2 concentration can improve the ˙OH generation, and thereby the anticancer effect of CDT and nanocatalytic therapy. 46 In addition, high valence ions such as Fe 3+ and Cu 2+ can scavenge intracellular ROS, 51,230,231 further amplifying oxidative stress and damage. 232 In the context of CDT, metal peroxide (CuO 2 , 56,230,233 CaO 2 , 234–236 etc .)…”

“…Dai et al designed pH/ROS cascade-responsive polymeric prodrug micelles for the synergistic inhibition of cancer and reversal of drug resistance, where the pH-responsive charge reversal facilitated cellular uptake and the removal of CPT by ROS upregulation could transform the hydrophobic core to hydrophilic, and then the disassembly of the micelles, which facilitated rapid drug release. 212 Besides Lapa, other biological molecules (such cinnamaldehyde) have been utilized to enable ROS-enhanced CT. 51,213 Various drug carriers with ROS-sensitive moieties, such as thioketal (TK), boronic ester, and alkylene sulfide, have been developed to co-deliver these ROS-generating molecules and chemotherapeutic agents for ROS upregulation-activated, tumor-specific chemotherapy. 214,215 We developed an ROSresponsive and ROS-regenerative system based on CAembedded polymer NPs, where CA was released upon thioacetal breakdown in response to ROS for ROS regeneration.…”