Despite the considerable potentiality of photodynamic therapy(PDT)in cancer treatment,conventional hydrophobic photosensitizers cause obstacles for in vivo application,while their inert structures are difficult to che...Despite the considerable potentiality of photodynamic therapy(PDT)in cancer treatment,conventional hydrophobic photosensitizers cause obstacles for in vivo application,while their inert structures are difficult to chemically modify.Additionally,undesirable tumor hypoxia resulting from oxygen consumption also discounts the therapeutic efficacy of PDT.Herein,we developed a self-strengthened nanogel with reactive oxygen species(ROS)trigger-explosive property.IR780 was spontaneous assembled within the conical cavity of cyclodextrin(β-CD)using host-vip interactions,while adjacent IR780 molecules on the dextrin backbone with hydrophobic interaction andπconjugation induced nanogel formation.Simultaneously,hydrophilic compound tirapazamine(TPZ)was incorporated into nanogel for synergistic tumor treatment.The inherent high levels of ROS in tumor can break down boronic ester bond linker of nanogel,initiating its disintegration.Furthermore,our findings indicate the ROS level(including H2O2and1O2)can be transiently enhanced during PDT process at the animal level,which accelerates the explosion of nanogel.Notably,the IR780@β-CD module exhibited enhanced ROS generation efficiency during PDT with the continues explosion of nanogel,which further strengthens nanogel disintegration,tumor phototherapy and cargo releasement.Additionally,the released TPZ is activated under hypoxic conditions after PDT treatment,addressing the limitations of PDT and facilitating multi-synergistic tumor treatment.展开更多
基金financially supported by the National Natural Science Foundation of China(No.82102908)the Natural Science Foundation of Tianjin of China(No.22JCQNJC01260)+3 种基金Natural Science Foundation of Hebei Province of China(No.H2024202004)National Natural Science Foundation of China(No.U23A6008)National Key Research and Development Program of China(No.2023YFC2412300)Natural Science Foundation of Hebei Province of China(No.H2022202007)。
文摘Despite the considerable potentiality of photodynamic therapy(PDT)in cancer treatment,conventional hydrophobic photosensitizers cause obstacles for in vivo application,while their inert structures are difficult to chemically modify.Additionally,undesirable tumor hypoxia resulting from oxygen consumption also discounts the therapeutic efficacy of PDT.Herein,we developed a self-strengthened nanogel with reactive oxygen species(ROS)trigger-explosive property.IR780 was spontaneous assembled within the conical cavity of cyclodextrin(β-CD)using host-vip interactions,while adjacent IR780 molecules on the dextrin backbone with hydrophobic interaction andπconjugation induced nanogel formation.Simultaneously,hydrophilic compound tirapazamine(TPZ)was incorporated into nanogel for synergistic tumor treatment.The inherent high levels of ROS in tumor can break down boronic ester bond linker of nanogel,initiating its disintegration.Furthermore,our findings indicate the ROS level(including H2O2and1O2)can be transiently enhanced during PDT process at the animal level,which accelerates the explosion of nanogel.Notably,the IR780@β-CD module exhibited enhanced ROS generation efficiency during PDT with the continues explosion of nanogel,which further strengthens nanogel disintegration,tumor phototherapy and cargo releasement.Additionally,the released TPZ is activated under hypoxic conditions after PDT treatment,addressing the limitations of PDT and facilitating multi-synergistic tumor treatment.
