Although anti-cancer nanotherapeutics have made breakthroughs,many remain clinically unsatisfactory due to limited delivery efficiency and complicated biological barriers.Here,we prepared charge-reversible crosslinked...Although anti-cancer nanotherapeutics have made breakthroughs,many remain clinically unsatisfactory due to limited delivery efficiency and complicated biological barriers.Here,we prepared charge-reversible crosslinked nanoparticles(PDC NPs)by supramolecular self-assembly of pro-apoptotic peptides and photosensitizers,followed by crosslinking the self-assemblies with polyethylene glycol to impart tumor microenvironment responsiveness and charge-reversibility.The resultant PDC NPs have a high drug loading of 68.3%,substantially exceeding that of 10%–15%in conventional drug delivery systems.PDC NPs can overcome the delivery hurdles to significantly improve the tumor accumulation and endocytosis of payloads by surface charge reversal and responsive crosslinking strategy.Pro-apoptotic peptides target the mitochondrial membranes and block the respiratory effect to reduce local oxygen consumption,which extensively augments oxygen-dependent photodynamic therapy(PDT).The photosensitizers around mitochondria increased along with the peptides,allowing PDT to work with pro-apoptotic peptides synergistically to induce tumor cell death by mitochondria-dependent apoptotic pathways.Our strategy would provide a valuable reference for improving the delivery efficiency of hydrophilic peptides and developing mitochondrial-targeting cancer therapies.展开更多
Extensive research have been devoted to the exploration of multifunctional theranostic agents for cancer,but the poor tumor specificity and unsatisfactory treatment efficacy are some of the critical obstacles for thei...Extensive research have been devoted to the exploration of multifunctional theranostic agents for cancer,but the poor tumor specificity and unsatisfactory treatment efficacy are some of the critical obstacles for their clinical translations.Herein,ferrocene-carbon dot-crosslinked nanoparticles(Fc-CD NPs)were designed and fabricated for achieving highly specific and photothermal-augmented chemodynamic therapy(CDT).The Fc-CD NPs were found not only to inherit the immanent fluorescence,photoacoustic,and photothermal properties of carbon dots(CDs),but also be endowed with CDT that could occur selectively in tumor microenvironment(TME)due to the presence of Fc for triggering Fenton reaction.Moreover,the enlarged particle size of Fc-CD NPs facilitated their effective accumulation at tumor sites,thus realizing great improvement for antitumor treatment outcomes.Once docking at tumor and being exposed to 660 nm laser irradiation,significantly amplified CDT effect of Fc-CD NPs was observed due to heataccelerating generation of reactive oxygen species(ROS).More interestingly,since the produced ROS could in turn alleviate the thermal-resistance of photothermal therapy(PTT),the therapeutic efficiency of integrated PTT and CDT was synergized to the maximum extent.This study on the one hand provides a facile approach to fabricate CDs-based multifunctional theranostic nanoplatform with enhanced tumor accumulation and specificity,on the other hand emphasizes the merits of synergizing mutually beneficial therapeutic modalities for more efficient cancer therapy.展开更多
基金support from the National Natural Science Foundation of China(Nos.82172084 and 81803002)STI2030-Major Projects(No.2022ZD0212500)。
文摘Although anti-cancer nanotherapeutics have made breakthroughs,many remain clinically unsatisfactory due to limited delivery efficiency and complicated biological barriers.Here,we prepared charge-reversible crosslinked nanoparticles(PDC NPs)by supramolecular self-assembly of pro-apoptotic peptides and photosensitizers,followed by crosslinking the self-assemblies with polyethylene glycol to impart tumor microenvironment responsiveness and charge-reversibility.The resultant PDC NPs have a high drug loading of 68.3%,substantially exceeding that of 10%–15%in conventional drug delivery systems.PDC NPs can overcome the delivery hurdles to significantly improve the tumor accumulation and endocytosis of payloads by surface charge reversal and responsive crosslinking strategy.Pro-apoptotic peptides target the mitochondrial membranes and block the respiratory effect to reduce local oxygen consumption,which extensively augments oxygen-dependent photodynamic therapy(PDT).The photosensitizers around mitochondria increased along with the peptides,allowing PDT to work with pro-apoptotic peptides synergistically to induce tumor cell death by mitochondria-dependent apoptotic pathways.Our strategy would provide a valuable reference for improving the delivery efficiency of hydrophilic peptides and developing mitochondrial-targeting cancer therapies.
基金the National Natural Science Foundation of China(Nos.52173126,51902323,51872300,32101142,and U1832110).
文摘Extensive research have been devoted to the exploration of multifunctional theranostic agents for cancer,but the poor tumor specificity and unsatisfactory treatment efficacy are some of the critical obstacles for their clinical translations.Herein,ferrocene-carbon dot-crosslinked nanoparticles(Fc-CD NPs)were designed and fabricated for achieving highly specific and photothermal-augmented chemodynamic therapy(CDT).The Fc-CD NPs were found not only to inherit the immanent fluorescence,photoacoustic,and photothermal properties of carbon dots(CDs),but also be endowed with CDT that could occur selectively in tumor microenvironment(TME)due to the presence of Fc for triggering Fenton reaction.Moreover,the enlarged particle size of Fc-CD NPs facilitated their effective accumulation at tumor sites,thus realizing great improvement for antitumor treatment outcomes.Once docking at tumor and being exposed to 660 nm laser irradiation,significantly amplified CDT effect of Fc-CD NPs was observed due to heataccelerating generation of reactive oxygen species(ROS).More interestingly,since the produced ROS could in turn alleviate the thermal-resistance of photothermal therapy(PTT),the therapeutic efficiency of integrated PTT and CDT was synergized to the maximum extent.This study on the one hand provides a facile approach to fabricate CDs-based multifunctional theranostic nanoplatform with enhanced tumor accumulation and specificity,on the other hand emphasizes the merits of synergizing mutually beneficial therapeutic modalities for more efficient cancer therapy.
