Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focus...Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.展开更多
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LY24H300001)the Medical and Health Research Project of Zhejiang Province(KY202302130009)National Health Service Research Project(WKZX2024CX501205).
文摘Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.
