In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy.In this study,a novel pH-responsive nanosystem is proposed for real-time monitoring of dru...In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy.In this study,a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy(SERS).The Fe3O4@Au@Ag nanoparticles(NPs)deposited graphene oxide(GO)nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid(4-MPBA)to form SERS probes(GO-Fe3O4@Au@Ag-MPBA).Furthermore,doxorubicin(DOX)is attached to SERS probes through a pH-responsive linker boronic ester(GO-Fe3O4@Au@Ag-MPBA-DOX),accompanying the 4-MPBA signal change in SERS.After the entry into tumor,the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal.Thus,the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra.Additionally,the strong T2 magnetic resonance(MR)signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy(PTT).Altogether,this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting,pH-sensitive drug release,SERS-traceable detection and MR imaging,endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.展开更多
Gynecological cancers present significant treatment challenges due to drug resistance and adverse side effects.This review explores advancements in lysosomal escape mechanisms,essential for enhancing nano-therapeutic ...Gynecological cancers present significant treatment challenges due to drug resistance and adverse side effects.This review explores advancements in lysosomal escape mechanisms,essential for enhancing nano-therapeutic efficacy.Strategies such as pH-sensitive linkers and membrane fusion are examined,showcasing their potential to improve therapeutic outcomes in ovarian,cervical,and uterine cancers.We delve into novel materials and strategies developed to bypass the lysosomal barrier,including pH-sensitive linkers,fusogenic lipids,and nanoparticles(NPs)engineered for endosomal disruption.Mechanisms such as the proton sponge effect,where NPs induce osmotic swelling and rupture of the lysosomal membrane,and membrane fusion,which facilitates the release of therapeutic agents directly into the cytoplasm,are explored in detail.These innovations not only promise to improve therapeutic outcomes but also minimize side effects,marking a significant step forward in the treatment of ovarian,cervical,and uterine cancers.By providing a comprehensive analysis of current advancements and their implications for clinical applications,this review sheds light on the potential of lysosomal escape strategies to revolutionize gynecological cancer treatment,setting the stage for future research and development in this vital area.展开更多
A polymeric polyethylenimine(PEI)-based prodrug of anticancer doxorubicin(DOX)(PEI-hyd-DOX) was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug ...A polymeric polyethylenimine(PEI)-based prodrug of anticancer doxorubicin(DOX)(PEI-hyd-DOX) was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug co-delivery in response to the intracellular acid microenvironments in the late endosome/lysosome compartments. The cytotoxicity of PEI-hyd-DOX was evaluated by the MTT assay and the cellular uptake was monitored using confocal laser scanning microscopy. The polymeric prodrug can respond with a high sensitivity to the specific acid condition inside cells, thus permitting the precise biocontrol over intracellular drug liberation with high drug efficacy. The chemical attachment of drug molecules also led to the relatively reduced toxicity and the enhanced transfection efficiency compared with parent PEI. The resulting data adumbrated the potential of PEI-hyd-DOX to co-deliver DOX and therapeutic gene for the combination of chemotherapy and gene therapy.展开更多
基金supported by the National Natural Science Foundation of China(81872759 and 22177039)the National Key Research and Development Program of China(2021YFC2300400)+1 种基金Scien ceand Technology Program of Guangzhou(202102010097,China)Pearl River Talent Program(2017GC010363,China).
文摘In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy.In this study,a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy(SERS).The Fe3O4@Au@Ag nanoparticles(NPs)deposited graphene oxide(GO)nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid(4-MPBA)to form SERS probes(GO-Fe3O4@Au@Ag-MPBA).Furthermore,doxorubicin(DOX)is attached to SERS probes through a pH-responsive linker boronic ester(GO-Fe3O4@Au@Ag-MPBA-DOX),accompanying the 4-MPBA signal change in SERS.After the entry into tumor,the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal.Thus,the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra.Additionally,the strong T2 magnetic resonance(MR)signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy(PTT).Altogether,this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting,pH-sensitive drug release,SERS-traceable detection and MR imaging,endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.
文摘Gynecological cancers present significant treatment challenges due to drug resistance and adverse side effects.This review explores advancements in lysosomal escape mechanisms,essential for enhancing nano-therapeutic efficacy.Strategies such as pH-sensitive linkers and membrane fusion are examined,showcasing their potential to improve therapeutic outcomes in ovarian,cervical,and uterine cancers.We delve into novel materials and strategies developed to bypass the lysosomal barrier,including pH-sensitive linkers,fusogenic lipids,and nanoparticles(NPs)engineered for endosomal disruption.Mechanisms such as the proton sponge effect,where NPs induce osmotic swelling and rupture of the lysosomal membrane,and membrane fusion,which facilitates the release of therapeutic agents directly into the cytoplasm,are explored in detail.These innovations not only promise to improve therapeutic outcomes but also minimize side effects,marking a significant step forward in the treatment of ovarian,cervical,and uterine cancers.By providing a comprehensive analysis of current advancements and their implications for clinical applications,this review sheds light on the potential of lysosomal escape strategies to revolutionize gynecological cancer treatment,setting the stage for future research and development in this vital area.
基金supported by the National Natural Science Foundation of China (21374085, 21174110, 51233003)the Natural Science Foundation of Hubei Province of China (2014CFB697)the Fundamental Research Funds for the Central Universities (2042014kf0193)
文摘A polymeric polyethylenimine(PEI)-based prodrug of anticancer doxorubicin(DOX)(PEI-hyd-DOX) was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug co-delivery in response to the intracellular acid microenvironments in the late endosome/lysosome compartments. The cytotoxicity of PEI-hyd-DOX was evaluated by the MTT assay and the cellular uptake was monitored using confocal laser scanning microscopy. The polymeric prodrug can respond with a high sensitivity to the specific acid condition inside cells, thus permitting the precise biocontrol over intracellular drug liberation with high drug efficacy. The chemical attachment of drug molecules also led to the relatively reduced toxicity and the enhanced transfection efficiency compared with parent PEI. The resulting data adumbrated the potential of PEI-hyd-DOX to co-deliver DOX and therapeutic gene for the combination of chemotherapy and gene therapy.
