Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as ce...Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably throm-bosis.Furthermore,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting mechanism.Hence,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive chemosensitization.On one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP chemotherapy.Simultaneously,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA repair.In essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation of China(No.2021A1515011050)President Foundation of the Third Affiliated Hospital of Southern Medical University(No.YM202202)+1 种基金the Health Economics Association Research Program of Guangdong Province(No.2022-WJZD-20)the Higher Education Teaching Management Association Curriculum Thinking and Administration Program of Guangdong Province(No.X-KCSZ2021082).
文摘Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably throm-bosis.Furthermore,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting mechanism.Hence,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive chemosensitization.On one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP chemotherapy.Simultaneously,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA repair.In essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.
