Most photodynamic therapies(PDT)rely on reactive oxygen species(ROS)produced by type II mecha nisms.However,since the production of type I ROS is not limited by oxygen content,making it more favorable for antimicrobia...Most photodynamic therapies(PDT)rely on reactive oxygen species(ROS)produced by type II mecha nisms.However,since the production of type I ROS is not limited by oxygen content,making it more favorable for antimicrobial phototherapy in complex microenvironments.Herein,we report a substituen cationization design strategy that not only improves the hydrophilicity of the prepared phthalocyanine molecule,but also promotes the electron transfer process in the photosensitizer,resulting in the strong type I photodynamic effect of the phthalocyanine self-assembled photosensitizer to efficiently generate O_(2)^(·-)under both normal and hypoxic conditions.This in combination with its excellent bacteria recogni tion capability derived from the cationic part on its surface and intrinsic photothermal therapy effect o the phthalocyanine macrocycle endows the phthalocyanine self-assembled photosensitizer with excellen phototherapeutic antimicrobial properties in preclinical models,effectively promoting the wound healing process.This work provides a promising strategy for designing efficient multi-mode photosensitizers.展开更多
Despite advancements in lipid droplet(LD)-targeted photosensitizers(PSs),critical challenges persist in achieving deep-tissue penetration,overcoming tumor hypoxic resistance,and coordinating multimodal cell death path...Despite advancements in lipid droplet(LD)-targeted photosensitizers(PSs),critical challenges persist in achieving deep-tissue penetration,overcoming tumor hypoxic resistance,and coordinating multimodal cell death pathways.To address these limitations,a molecular engineering strategy was introduced to construct a series of aggregation-induced emission(AIE)PSs(MOITP,MOITM,and MOITT),which exhibited near-infrared(NIR)emission.The strong electronwithdrawing capability of the acceptor moiety in MOITT resulted in a bathochromic shift in absorption(606 nm)and NIR-Ⅱ emission(1080 nm).Under 808 nm laser irradiation,MOITT exhibited the strongest type Ⅰ reactive oxygen species generation and the highest photothermal conversion efficiency(η=44%).Notably,MOITT nanoparticles(NPs)showed efficient cellular internalization and selective accumulation in LDs.Upon laser irradiation,phototherapy mediated by MOITT NPs initiated lipid peroxidation,triggering ferroptosis while synergistically inducing apoptosis.In vivo studies demonstrated that MOITT NPs enabled high-resolution NIRⅡ fluorescence imaging of blood vessels and effective imagingguided phototherapy to eradicate tumors.This work establishes a novel paradigm for spatiotemporal control of cancer therapy through organelle-specific multimodal cell death integration.展开更多
Various obstacles[poor tissue penetration,hypoxic tumor microenvironment,and reactive oxygen species(ROS)production quenching due to aggregation]obstruct imaging-guided high-efficiency phototherapy targeting tumors.He...Various obstacles[poor tissue penetration,hypoxic tumor microenvironment,and reactive oxygen species(ROS)production quenching due to aggregation]obstruct imaging-guided high-efficiency phototherapy targeting tumors.Herein,nanophthalocyanine(ZnPcN4-TF)is elaborately designed based on a synthetic phthalocyanine derivative(ZnPcN4)and nonimmunogenic transferrin(TF)through multiple noncovalent interactions for photoacoustic(PA)imaging-guided phototherapy.By conjugating electron-rich amino groups effectively suppressed fluorescence and ROS generation due to the strong photoinduced electron transfer effect,ZnPcN4 became an ideal photothermal and PA imaging agent.ZnPcN4-TF not only effectively targeted tumor sites and accumulated there,but also,surprisingly,facilitated the enhancement of ROS production via a type I process in an aggregate compared to ZnPcN4 itself,potentially due to accelerated electron transfer.Simultaneously,ZnPcN4-TF had a substantially more powerful photothermal effect than ZnPcN4 itself.Thus,this design effectively overcomes the obstacles to photodynamic therapy(aggregation-related ROS generation quenching in a hypoxic environment).Furthermore,PA imaging solves the tissue penetration challenge in optical imaging.This study provides a broader base for designing novel photosensitizers to improve phototherapy under hypoxia.展开更多
基金supported by the Central Guidance on the Local Science and Technology Development Fund of Guangxi Province(No.Gui Ke ZY22096010)Guangxi Natural Science Fundation(No.2023GXNSFAA026181)+1 种基金National Natural Science Foundation of China(No.51961009)BAGUI Scholar Program,Guangxi Province,China。
文摘Most photodynamic therapies(PDT)rely on reactive oxygen species(ROS)produced by type II mecha nisms.However,since the production of type I ROS is not limited by oxygen content,making it more favorable for antimicrobial phototherapy in complex microenvironments.Herein,we report a substituen cationization design strategy that not only improves the hydrophilicity of the prepared phthalocyanine molecule,but also promotes the electron transfer process in the photosensitizer,resulting in the strong type I photodynamic effect of the phthalocyanine self-assembled photosensitizer to efficiently generate O_(2)^(·-)under both normal and hypoxic conditions.This in combination with its excellent bacteria recogni tion capability derived from the cationic part on its surface and intrinsic photothermal therapy effect o the phthalocyanine macrocycle endows the phthalocyanine self-assembled photosensitizer with excellen phototherapeutic antimicrobial properties in preclinical models,effectively promoting the wound healing process.This work provides a promising strategy for designing efficient multi-mode photosensitizers.
基金supported by the National Natural Science Foundation of China (22077077, 22275119, 21975149, and 21672135)the Fundamental Research Funds for the Central Universities (GK202301010, 18QNGG007, and 2021TS033)。
文摘Despite advancements in lipid droplet(LD)-targeted photosensitizers(PSs),critical challenges persist in achieving deep-tissue penetration,overcoming tumor hypoxic resistance,and coordinating multimodal cell death pathways.To address these limitations,a molecular engineering strategy was introduced to construct a series of aggregation-induced emission(AIE)PSs(MOITP,MOITM,and MOITT),which exhibited near-infrared(NIR)emission.The strong electronwithdrawing capability of the acceptor moiety in MOITT resulted in a bathochromic shift in absorption(606 nm)and NIR-Ⅱ emission(1080 nm).Under 808 nm laser irradiation,MOITT exhibited the strongest type Ⅰ reactive oxygen species generation and the highest photothermal conversion efficiency(η=44%).Notably,MOITT nanoparticles(NPs)showed efficient cellular internalization and selective accumulation in LDs.Upon laser irradiation,phototherapy mediated by MOITT NPs initiated lipid peroxidation,triggering ferroptosis while synergistically inducing apoptosis.In vivo studies demonstrated that MOITT NPs enabled high-resolution NIRⅡ fluorescence imaging of blood vessels and effective imagingguided phototherapy to eradicate tumors.This work establishes a novel paradigm for spatiotemporal control of cancer therapy through organelle-specific multimodal cell death integration.
基金supported by the National Natural Science Foundation of China(grant nos.T2322004 and 22078066)Science Research Project of Hebei Education Department(grant no.QN2025122)+5 种基金the Hebei Natural Science Foundation(grant no.B2024208046)the Basic Science Research Program through the National Research Foundation of Korea(NRF)grant funded by the Korean government(Ministry of Science and ICT(MSIT))(grant no.2022R1A2C3005420)the Basic Science Research Program through the NRF funded by the Ministry of Education(grant no.2020R1A6A1A03047902)National R&D Program through the NRF funded by the MSIT(grant no.2023R1A2C_(3)004880)BK21 FOUR projects(POSTECH)the NRF grant funded by the Korean government(MSIT)(grant no.2022R1A3B1077354)。
文摘Various obstacles[poor tissue penetration,hypoxic tumor microenvironment,and reactive oxygen species(ROS)production quenching due to aggregation]obstruct imaging-guided high-efficiency phototherapy targeting tumors.Herein,nanophthalocyanine(ZnPcN4-TF)is elaborately designed based on a synthetic phthalocyanine derivative(ZnPcN4)and nonimmunogenic transferrin(TF)through multiple noncovalent interactions for photoacoustic(PA)imaging-guided phototherapy.By conjugating electron-rich amino groups effectively suppressed fluorescence and ROS generation due to the strong photoinduced electron transfer effect,ZnPcN4 became an ideal photothermal and PA imaging agent.ZnPcN4-TF not only effectively targeted tumor sites and accumulated there,but also,surprisingly,facilitated the enhancement of ROS production via a type I process in an aggregate compared to ZnPcN4 itself,potentially due to accelerated electron transfer.Simultaneously,ZnPcN4-TF had a substantially more powerful photothermal effect than ZnPcN4 itself.Thus,this design effectively overcomes the obstacles to photodynamic therapy(aggregation-related ROS generation quenching in a hypoxic environment).Furthermore,PA imaging solves the tissue penetration challenge in optical imaging.This study provides a broader base for designing novel photosensitizers to improve phototherapy under hypoxia.
