Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing ...Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing to its minimal invasiveness,localized tumor damage,and high safety profile.However,its efficacy is limited by poor stability of photosensitizers,inadequate tumor accumulation,and a complex tumor microenvironment.To overcome these challenges,extensive endeavors have been made to explore the co-assembly of the widely used photosensitizer chlorin e6(Ce6)with various functional small molecules to enhance pharmacodynamic activity.This review provides a comprehensive overview of current studies on Ce6-based nanoparticles for effective PDT and precise delivery of functional molecules.The self-assembly mechanism will be discussed in detail,with a focus on potential strategies for combinational therapy with PDT.展开更多
Glioblastoma(GBM)is the most aggressive malignant brain tumor and has a high mortality rate.Photodynamic therapy(PDT)has emerged as a promising approach for the treatment of malignant brain tumors.However,the use of P...Glioblastoma(GBM)is the most aggressive malignant brain tumor and has a high mortality rate.Photodynamic therapy(PDT)has emerged as a promising approach for the treatment of malignant brain tumors.However,the use of PDT for the treatment of GBM has been limited by its low blood-brain barrier(BBB)permeability and lack of cancer-targeting ability.Herein,brain endothelial cell-derived extracellular vesicles(bEVs)were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB.To enhance PDT efficacy,the photosensitizer chlorin e6(Ce6)was linked to mitochondria-targeting triphenylphosphonium(TPP)and entrapped into bEVs.TPPconjugated Ce6(TPP-Ce6)selectively accumulated in the mitochondria,which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation.Moreover,the encapsulation of TPP-Ce6 into b EVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6,leading to significantly enhanced PDT efficacy in U87MG GBM cells.An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that b EVs containing TPP-Ce6[b EV(TPP-Ce6)]substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis.As such,b EV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity,suggesting that mitochondria are an effective target for photodynamic GBM therapy.展开更多
Photodynamic therapy (PDT), as a noninvasive therapeutic method, has been actively explored recently for cancer treatment. However, owing to the weak absorption in the optically transparent windows of biological tis...Photodynamic therapy (PDT), as a noninvasive therapeutic method, has been actively explored recently for cancer treatment. However, owing to the weak absorption in the optically transparent windows of biological tissues, most com- mercial photosensitizers (PSs) exhibit low singlet oxygen (^1O2) quantum yields when excited by light within this window. Finding the best way to boost ^1O2 production for clinical applications using light sources within this window is, thus, a great challenge. Herein, we tackle this problem using plasmon resonance energy transfer (PRET) from plasmonic nanoparticles (NPs) to PSs and demonstrate that the formation of plasmon quenching dips is an effective way to enhance ^1O2 generation. The combination of the photosensitizer chlorin e6 (Ce6) and gold nanorods (AuNR) was employed as a model system. We observed a clear quenching dip in the longitudinal surface plasmon resonance (LSPR) band of the AuNRs when the LSPR band overlaps with the Q band of Ce6 and the spacing between Ce6 and the rods is within the acting distance of PRET. Upon irradiation with 660 nm continuous-wave laser light, we obtained a seven-fold enhancement in the ^1O2 signal intensity compared with that of a non-PRET sample, as determined using the ^1O2 electron spin resonance probe 2,2,6,6-tetramethyl-4-piperidine (TEMP). Furthermore, we demonstrated that the PRET effect is more efficient in enhancing ^1O2 yield than the often-employed local field enhancement effect. The effectiveness of PRET is further extended to the in vitro level. Considering the flexibility in manipulating the localized SPR properties of plasmonic nanoparticles/nanostructures, our findings suggest that PRET-based strategies may be a general way to overcome the deficiency of most commercial organic PSs in biological optically transparent windows and promote their applications in clinical tumor treatments.展开更多
Cholangiocellular cancer(CCC)is an oncological disease of the bile ducts characterized by a high mortality rate.To date,the use of standard methods for the diagnosis and treatment of CCC has not been able to reduce mo...Cholangiocellular cancer(CCC)is an oncological disease of the bile ducts characterized by a high mortality rate.To date,the use of standard methods for the diagnosis and treatment of CCC has not been able to reduce mortality from this disease.This work presents the results of fluorescence diagnostics(FD),which consists in using a modified optical fiber and photodynamic therapy(PDT)using a therapeutic laser instead of a low-intensity laser.This technique was tested on 43 patients in a clinical setting.The results obtained indicate a direct correlation between spectroscopic and video FD methods.Furthermore,a direct correlation was found between the photobleaching of a chlorin e6-based photosensitizer,with the commercial names of PhotoIon Radachlorin and Photoran and stricture regression.Our findings demonstrate the possibility of using a therapeutic laser with a wavelength of 660 nm for both diagnosis and treatment of bile ducts cancer,which results in a significant reduction of the operation time without decreasing its effectiveness.展开更多
Reactive oxygen species(ROS)are byproducts of cellular metabolism;they play a significant role as secondary messengers in cell signaling.In cells,high concentrations of ROS induce apoptosis,senescence,and contact inhi...Reactive oxygen species(ROS)are byproducts of cellular metabolism;they play a significant role as secondary messengers in cell signaling.In cells,high concentrations of ROS induce apoptosis,senescence,and contact inhibition,while low concentrations of ROS result in angiogenesis,proliferation,and cytoskeleton remodeling.Thus,controlling ROS generation is an important factor in cell biology.We designed a chlorin e6(Ce6)-immobilized polyethylene terephthalate(PET)film(Ce6-PET)to produce extracellular ROS under red-light irradiation.The application of Ce6-PET films can regulate the generation of ROS by altering the intensity of light-emitting diode sources.We confirmed that the Ce6-PET film could effectively promote cell growth under irradiation at 500 μW/cm^(2) for 30 min in human umbilical vein endothelial cells.We also found that the Ce6-PET film is more efficient in generating ROS than a Ce6-incorporated polyurethane film under the same conditions.Ce6-PET fabrication shows promise for improving the localized delivery of extracellular ROS and regulating ROS formation through the optimization of irradiation intensity.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:82222903Li Ka Shing Faculty of Medicine(Start-up Fund)of The University of Hong Kong.
文摘Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing to its minimal invasiveness,localized tumor damage,and high safety profile.However,its efficacy is limited by poor stability of photosensitizers,inadequate tumor accumulation,and a complex tumor microenvironment.To overcome these challenges,extensive endeavors have been made to explore the co-assembly of the widely used photosensitizer chlorin e6(Ce6)with various functional small molecules to enhance pharmacodynamic activity.This review provides a comprehensive overview of current studies on Ce6-based nanoparticles for effective PDT and precise delivery of functional molecules.The self-assembly mechanism will be discussed in detail,with a focus on potential strategies for combinational therapy with PDT.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)[(NRF-2022R1A2C1007207,Korea)Basic Research Laboratory Program(NRF-2020R1A4A2002894,Korea)+3 种基金Basic Science Research Program(NRF-2020R1A2B5B01001719,Korea)Engineering Research Center of Excellence Program(NRF-2016R1A5A1010148,Korea)]supported by Basic Science Research Program through the NRF funded by the Ministry of Education(NRF-2021R1I1A1A01042149,Korea)support by the Brigham Research Institute,USA。
文摘Glioblastoma(GBM)is the most aggressive malignant brain tumor and has a high mortality rate.Photodynamic therapy(PDT)has emerged as a promising approach for the treatment of malignant brain tumors.However,the use of PDT for the treatment of GBM has been limited by its low blood-brain barrier(BBB)permeability and lack of cancer-targeting ability.Herein,brain endothelial cell-derived extracellular vesicles(bEVs)were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB.To enhance PDT efficacy,the photosensitizer chlorin e6(Ce6)was linked to mitochondria-targeting triphenylphosphonium(TPP)and entrapped into bEVs.TPPconjugated Ce6(TPP-Ce6)selectively accumulated in the mitochondria,which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation.Moreover,the encapsulation of TPP-Ce6 into b EVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6,leading to significantly enhanced PDT efficacy in U87MG GBM cells.An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that b EVs containing TPP-Ce6[b EV(TPP-Ce6)]substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis.As such,b EV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity,suggesting that mitochondria are an effective target for photodynamic GBM therapy.
基金This work was supported by the Ministry of Science and Technology of China (Nos. 2016YFA0200903 and 2011CB932802), and the National Natural Science Foundation of China (Nos. 91127013 and 21173056).
文摘Photodynamic therapy (PDT), as a noninvasive therapeutic method, has been actively explored recently for cancer treatment. However, owing to the weak absorption in the optically transparent windows of biological tissues, most com- mercial photosensitizers (PSs) exhibit low singlet oxygen (^1O2) quantum yields when excited by light within this window. Finding the best way to boost ^1O2 production for clinical applications using light sources within this window is, thus, a great challenge. Herein, we tackle this problem using plasmon resonance energy transfer (PRET) from plasmonic nanoparticles (NPs) to PSs and demonstrate that the formation of plasmon quenching dips is an effective way to enhance ^1O2 generation. The combination of the photosensitizer chlorin e6 (Ce6) and gold nanorods (AuNR) was employed as a model system. We observed a clear quenching dip in the longitudinal surface plasmon resonance (LSPR) band of the AuNRs when the LSPR band overlaps with the Q band of Ce6 and the spacing between Ce6 and the rods is within the acting distance of PRET. Upon irradiation with 660 nm continuous-wave laser light, we obtained a seven-fold enhancement in the ^1O2 signal intensity compared with that of a non-PRET sample, as determined using the ^1O2 electron spin resonance probe 2,2,6,6-tetramethyl-4-piperidine (TEMP). Furthermore, we demonstrated that the PRET effect is more efficient in enhancing ^1O2 yield than the often-employed local field enhancement effect. The effectiveness of PRET is further extended to the in vitro level. Considering the flexibility in manipulating the localized SPR properties of plasmonic nanoparticles/nanostructures, our findings suggest that PRET-based strategies may be a general way to overcome the deficiency of most commercial organic PSs in biological optically transparent windows and promote their applications in clinical tumor treatments.
基金This work was funded by RFBR according to the research project(Nos.17-00-00162 and 17-00-00159).
文摘Cholangiocellular cancer(CCC)is an oncological disease of the bile ducts characterized by a high mortality rate.To date,the use of standard methods for the diagnosis and treatment of CCC has not been able to reduce mortality from this disease.This work presents the results of fluorescence diagnostics(FD),which consists in using a modified optical fiber and photodynamic therapy(PDT)using a therapeutic laser instead of a low-intensity laser.This technique was tested on 43 patients in a clinical setting.The results obtained indicate a direct correlation between spectroscopic and video FD methods.Furthermore,a direct correlation was found between the photobleaching of a chlorin e6-based photosensitizer,with the commercial names of PhotoIon Radachlorin and Photoran and stricture regression.Our findings demonstrate the possibility of using a therapeutic laser with a wavelength of 660 nm for both diagnosis and treatment of bile ducts cancer,which results in a significant reduction of the operation time without decreasing its effectiveness.
基金This work was supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT,Nos 2017M3A9B3063638 and 2019R1A2C2005256).
文摘Reactive oxygen species(ROS)are byproducts of cellular metabolism;they play a significant role as secondary messengers in cell signaling.In cells,high concentrations of ROS induce apoptosis,senescence,and contact inhibition,while low concentrations of ROS result in angiogenesis,proliferation,and cytoskeleton remodeling.Thus,controlling ROS generation is an important factor in cell biology.We designed a chlorin e6(Ce6)-immobilized polyethylene terephthalate(PET)film(Ce6-PET)to produce extracellular ROS under red-light irradiation.The application of Ce6-PET films can regulate the generation of ROS by altering the intensity of light-emitting diode sources.We confirmed that the Ce6-PET film could effectively promote cell growth under irradiation at 500 μW/cm^(2) for 30 min in human umbilical vein endothelial cells.We also found that the Ce6-PET film is more efficient in generating ROS than a Ce6-incorporated polyurethane film under the same conditions.Ce6-PET fabrication shows promise for improving the localized delivery of extracellular ROS and regulating ROS formation through the optimization of irradiation intensity.