Cinnamaldehyde-based poly(thioacetal): A ROS-awakened self-amplifying degradable polymer for enhanced cancer immunotherapy

Reactive oxygen species-upregulating nanomedicines towards enhanced cancer therapy

“…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.…”

“…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.…”

Advanced Biomaterials with Intrinsic Immunomodulation Effects for Cancer Immunotherapy

“…[93] Yuan and coworkers reported a ROS-responsive self-amplifying degradable polymer, poly(thioacetal), which could trigger the ICD of cancer cells itself. [94] Upon uptake by cancer cells, poly(thioacetal) could release cinnamaldehyde after ROS-triggered degradation to elevate the intracellular ROS through mitochondrial dysfunction. The resulting oxidative stress of cancer cells induced ICD, with exposure of CRT on the cells surface and secretion of HMGB1 NPs treatment highly inhibits the growth of both primary and distant tumors in bilateral CT26 tumor-bearing mice as well as prolongs the survival rate.…”

Biomaterials That Induce Immunogenic Cell Death

“…[16] Since producing reactive oxygen species (ROS) is an essential means of causing ER stress, researchers have designed several ROS-responsive polymers as ICD inducers. [17][18][19] Inorganic nano-modulators (e.g., Ca 2+ , Fe 2+ , Mn 2+ , and NO) induce ICD by targeting different intracellular organelles. [20][21][22][23] Here, we review how organic and inorganic biomaterials induce ICD in the tumor cells to address the current limitations of immunotherapy (Scheme 1).…”