The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing...The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies.This study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’sensitivity.The extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C_(20) can balance efficacy and safety.These results provide a great reference for the rational design of prodrug nanoassemblies.展开更多
基金financially supported by National Key R&D Program of China(No.2022YFE0111600)National Natural Science Foundation of China(No.82272151 and 82204318)+2 种基金Doctoral Scientific Research Staring Foundation of Liaoning Province(No.2021-BS-130,China)General Program of Department of Education of Liaoning Province(No.LJKZ0953,China)Shenyang Young and Middle-aged Science and Technology Innovation Talents Support Program(RC220389,China)。
文摘The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies.This study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’sensitivity.The extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C_(20) can balance efficacy and safety.These results provide a great reference for the rational design of prodrug nanoassemblies.
