A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynami...A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.展开更多
Singlet oxygen(1 O2) plays an important role in various applications, such as in the photodynamic therapy(PDT) of cancers,photodynamic inactivation of microorganisms, photo-degradation of toxic compounds, and photo-ox...Singlet oxygen(1 O2) plays an important role in various applications, such as in the photodynamic therapy(PDT) of cancers,photodynamic inactivation of microorganisms, photo-degradation of toxic compounds, and photo-oxidation in synthetic chemistry. Recently,water-soluble metal nanoclusters(NCs) have been utilized as photosensitizers for the generation of highly reactive 1 O2 because of their high water solubility, low toxicity, and surface functionalizability for targeted substances. In the case of metal NC-based photosensitizers, the photo-physical properties depend on the core size of the NCs and the core/ligand interfacial structures. A wide range of atomically precise gold NCs have been reported; however, reports on the synthesis of atomically precise silver NCs are limited due to the high reactivity and low photostability(i.e., easy oxidation) of Ag NCs. In addition, there have been few reports on what kinds of metal NCs can generate large amounts of 1 O2. In this study, we developed a new one-pot synthesis method of water-soluble Ag7(MBISA)6(MBISA= 2-mercapto-5-benzimidazolesulfonic acid sodium salt) NCs with highly efficient 1 O2 generation ability under the irradiation of white light emitting diodes(LEDs). The molecular formula and purity were determined by electrospray ionization mass spectrometry and gel electrophoresis. To the best of our knowledge, this is the first report on atomically precise thiolate silver clusters(Agn(SR)m) for efficient 1 O2 generation under visible light irradiation. The 1 O2 generation efficiency of Ag7(MBISA)6 NCs was higher than those of the following known water-soluble metal NCs: bovine serum albumin(BSA)-Au25 NCs,BSA-Ag8 NCs, BSA-Ag14 NCs,Ag25(dihydrolipoic acid)14 NCs,Ag35(glutathione)18 NCs,and Ag75(glutathione)40 NCs. The metal NCs examined in this study showed the following order of 1 O2 generation efficiency under white light irradiation: Ag7(MBISA)6 > BSA-Ag14 > Ag75(SG)40 > Ag35(SG)18 >BSA-Au25 >>BSA-Ags(not detected) and Ag2 s(DHLA)14(not detected). For further improving the 1 O2 generation of Ag7(MBISA)6 NCs, we developed a novel fluorescence resonance energy transfer(FRET) system by conjugating Ag7(MBISA)6 NCs with quinacrine(QC)(molar ratio of Ag NCs to QC is 1 : 0.5). We observed the FRET process,from QC to Ag7(MBISA)6 NCs,occurring in the conjugate. That is,the QC works as a donor chromophore,while the Ag NCs work as an acceptor chromophore in the FRET process. The FRET-mediated process caused a 2.3-fold increase in 1 O2 generation compared to that obtained with Ag7(MBISA)6 NCs alone. This study establishes a general and simple strategy for improving the PDT activity of metal NC-based photosensitizers.展开更多
OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character ...OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character of apoferritin in different pH environments.The photophysical and photobiological properties of hypocrellin B-loaded apoferritin were measured.RESULETS HB molecules were successfully encapsulated within apoferritincavity.HB-AFT-NPs exhibited higher ROS productionthan free HB.Additionally,phototoxicity of HB-AFT NPs to MDA-MB-231 cells was significantly improved as compared to free HB.CONCLUSION Together these results demonstrate that hypocrellin B-loaded apoferritin might be a potential nanoscale photosensitizer.展开更多
OBJECTIVE To investigate the therapeutic efficiency of an endogenous enzyme-NQO1 activated hypericin in photodynamic therapy.METHODS An endogenous enzyme-NQO1 responsive photo sensitizer was designed and synthesized b...OBJECTIVE To investigate the therapeutic efficiency of an endogenous enzyme-NQO1 activated hypericin in photodynamic therapy.METHODS An endogenous enzyme-NQO1 responsive photo sensitizer was designed and synthesized by conjugating aquinonebased ligand to a natural photosensitizer derived from Chinese herb.The photophysical and photochemical properties were investigated through UV-visible and fluorescence spectrophotometer,and the photodynamic activity was evaluated with MTT assay.RESULTS An endogenous enzyme-NQO1 activated hypericin was prepared and fully characterized with various spectroscopic methods.The electronic absorption was almost the same with the free hypericin,indicating the introducing of the ligand to hypericin has little effect to its ground state,while there is almost no detected fluorescence and reactive oxygen species(ROS)generation in PBS solution indicating the introducing of the ligand can effectively quench the fluorescence emission and ROS generation.The in vitro study showed that both compounds have almost no dark toxicity,but they are highlyphotocytoxic with an IC50 less than 1μmol·L-1 against A549 cell lines indicating the modified compound can be activated in the intracellular environment.CONCLUSION A simple and efficient hypericin-based activated photosensitizer was prepared.The ROS generation was quenched in PBS solution and it would be activated inside A549 cell lines.It may be served as apromising tumor selective fluorescent probe and photosensitizer for targeted photodynamic therapy.展开更多
OBJECTIVE To explore the effect of connexin(Cx)40-formed gap junctional intercellular communication(GJIC)on Photofrin-photodynamic therapy(PDT)phototoxicity in Cx40-transfected He La cells and its potential mechanisms...OBJECTIVE To explore the effect of connexin(Cx)40-formed gap junctional intercellular communication(GJIC)on Photofrin-photodynamic therapy(PDT)phototoxicity in Cx40-transfected He La cells and its potential mechanisms.METHODS He La cell line stably transfected to express Cx40 was seeded at high and low cell density,respectively,to assess in vitro photosensitivity using CCK8 assay.Western blot assay was performed to detect the expression of Cx40.The intracellular ROS and Ca^(2+) concentrations were determined using flow cytometer.4-HNE and ceramide were measured using ELISA assay.RESULTS Cx40-composed GJ formation at high density enhances the phototoxicity of PhotofrinPDT.When the Cx40 is not expressed or Cx40 channels are blocked,the phototoxicity in high-density cultures substantially reduces,indicating that the enhanced PDT phototoxicity at high density is mediated by Cx40-composed GJIC.The GJIC-mediated increase in PDT phototoxicity was associated with ROS and calcium-mediated stress signaling pathways.CONCLUSION The work uniquely presents the ability of Cx40-composed GJIC to enhance the sensitivity of malignant cells to PDT,and indicates that maintenance or increase of Cx40-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency.展开更多
Malignant tumors and infectious diseases are two main threats to human beings.Photodynamic therapy(PDT)is an effective approach to treat malignancies and infections through the generation of reactive oxygen species(RO...Malignant tumors and infectious diseases are two main threats to human beings.Photodynamic therapy(PDT)is an effective approach to treat malignancies and infections through the generation of reactive oxygen species(ROS)of a non-toxic photodynamic drug(photosensitizing agent)upon light irradiation.PDT shows promising in treating areas where light can reach,for example,skin and cavities.To treat the problems on deep tissues,much evidence has accumulated in recent years suggesting that sonodynamic therapy(SDT),which eradicates malignant or infectious cells by ROS produced from the interaction of ultrasound energy and sonodynamic drug(sonosensitizing agent),has potential in treating diseases in deep tissues because ultrasound energy has deeper tissue penetration than light energy.Natural products are a valuable source for developing novel drugs.In recent years,we are focusing on developing novel and naturally occurring photodynamic and sonodynamic agents.We have found some active components from natural products,for example,curcumin and hypocrellin,have not only photodynamic activity and also sonodynamic activity in killing bacterial and tumor cells.This talk will briefly introduce two new technologies including photodynamic and sonodynamic therapy,and highlight the recent development in photodynamic and sonodynamic drugs from natural products or traditional Chinese medicines.Chemical modifications of the active compounds have also been attempted to achieve better results.展开更多
Corrole,a representative branch of porphyrin,has recently gained popularity.These molecules,viewed as ring‑contracted porphyrinoids containing direct pyrrole‑pyrrole linkages due to the absence of a meso‑carbon atom,e...Corrole,a representative branch of porphyrin,has recently gained popularity.These molecules,viewed as ring‑contracted porphyrinoids containing direct pyrrole‑pyrrole linkages due to the absence of a meso‑carbon atom,exhibit significant photo‑physicochemical properties that make them attractive for various applications.Herein,this review comprehensively discusses the remarkable properties of corrole complexes,as well as related structures and chelation properties.It further explores the biological applications of corrole complexes for in vivo imaging and anticancer therapy.Additionally,it addresses common research bottlenecks and challenges,providing insights into future potential applications in disease diagnosis and treatment.Generally,this review aims to illuminate the significance of corrole complexes and their promising biological applications.展开更多
OBJECTIVE Hypericin,a powerful naturally photosensitizer in photodynamic therapy(PDT),is suitable for treating skin diseases involving excess capillary proliferation.In the present study,we aimed to evaluate the skin ...OBJECTIVE Hypericin,a powerful naturally photosensitizer in photodynamic therapy(PDT),is suitable for treating skin diseases involving excess capillary proliferation.In the present study,we aimed to evaluate the skin penetrability of a topically applied hypericin,expecting reducing the risk of prolonged skin photosensitivity,which often occurs after systemic administration.METHODS The Franz diffusion cell assay was performed to evaluate different penetration enhancers.In vivo studies,fluorescence microscopy was performed to examine the distribution of hypericin in the skin,macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment.Immunohistochemistry was used to determine the expression of PECAM-1 in the treated skin.RESULTS 5% menthol facilitated hypericin penetrate the skin of nude mice most.The results of in vivo assays revealed that hypericin penetrated nude mice skin,spread to the dermis,and resulted in obvious photosensitivity reaction on the dermal capillaries.Moreover,skin injured by the photosensitive reaction induced by hypericin was replaced by normal skin 7 d after hypericin-PDT treatment.CONCLUSION Topical hypericin could penetrate nude mouse skin well and be great potential in PDT treatment of skin diseases.展开更多
文摘A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.
基金The project was supported by the JSPS KAKENH1, Japan (15H03520, 15H03526, and 26107719), and the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, Japan.
文摘Singlet oxygen(1 O2) plays an important role in various applications, such as in the photodynamic therapy(PDT) of cancers,photodynamic inactivation of microorganisms, photo-degradation of toxic compounds, and photo-oxidation in synthetic chemistry. Recently,water-soluble metal nanoclusters(NCs) have been utilized as photosensitizers for the generation of highly reactive 1 O2 because of their high water solubility, low toxicity, and surface functionalizability for targeted substances. In the case of metal NC-based photosensitizers, the photo-physical properties depend on the core size of the NCs and the core/ligand interfacial structures. A wide range of atomically precise gold NCs have been reported; however, reports on the synthesis of atomically precise silver NCs are limited due to the high reactivity and low photostability(i.e., easy oxidation) of Ag NCs. In addition, there have been few reports on what kinds of metal NCs can generate large amounts of 1 O2. In this study, we developed a new one-pot synthesis method of water-soluble Ag7(MBISA)6(MBISA= 2-mercapto-5-benzimidazolesulfonic acid sodium salt) NCs with highly efficient 1 O2 generation ability under the irradiation of white light emitting diodes(LEDs). The molecular formula and purity were determined by electrospray ionization mass spectrometry and gel electrophoresis. To the best of our knowledge, this is the first report on atomically precise thiolate silver clusters(Agn(SR)m) for efficient 1 O2 generation under visible light irradiation. The 1 O2 generation efficiency of Ag7(MBISA)6 NCs was higher than those of the following known water-soluble metal NCs: bovine serum albumin(BSA)-Au25 NCs,BSA-Ag8 NCs, BSA-Ag14 NCs,Ag25(dihydrolipoic acid)14 NCs,Ag35(glutathione)18 NCs,and Ag75(glutathione)40 NCs. The metal NCs examined in this study showed the following order of 1 O2 generation efficiency under white light irradiation: Ag7(MBISA)6 > BSA-Ag14 > Ag75(SG)40 > Ag35(SG)18 >BSA-Au25 >>BSA-Ags(not detected) and Ag2 s(DHLA)14(not detected). For further improving the 1 O2 generation of Ag7(MBISA)6 NCs, we developed a novel fluorescence resonance energy transfer(FRET) system by conjugating Ag7(MBISA)6 NCs with quinacrine(QC)(molar ratio of Ag NCs to QC is 1 : 0.5). We observed the FRET process,from QC to Ag7(MBISA)6 NCs,occurring in the conjugate. That is,the QC works as a donor chromophore,while the Ag NCs work as an acceptor chromophore in the FRET process. The FRET-mediated process caused a 2.3-fold increase in 1 O2 generation compared to that obtained with Ag7(MBISA)6 NCs alone. This study establishes a general and simple strategy for improving the PDT activity of metal NC-based photosensitizers.
基金The project supported by the general grant fund from Hong Kong Research Grant Committee(476912)Health and Medical Research Fund(13120442)Innovation and Technology Fund of Shenzhen(CXZZ20120619150627260)
文摘OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character of apoferritin in different pH environments.The photophysical and photobiological properties of hypocrellin B-loaded apoferritin were measured.RESULETS HB molecules were successfully encapsulated within apoferritincavity.HB-AFT-NPs exhibited higher ROS productionthan free HB.Additionally,phototoxicity of HB-AFT NPs to MDA-MB-231 cells was significantly improved as compared to free HB.CONCLUSION Together these results demonstrate that hypocrellin B-loaded apoferritin might be a potential nanoscale photosensitizer.
基金The project supported by the general grant fund from Hong Kong Research Grant Committee(476912)Health and Medical Research Fund(13120442)Innovation and Technology Fund of Shenzhen(CXZZ20120619150627260)
文摘OBJECTIVE To investigate the therapeutic efficiency of an endogenous enzyme-NQO1 activated hypericin in photodynamic therapy.METHODS An endogenous enzyme-NQO1 responsive photo sensitizer was designed and synthesized by conjugating aquinonebased ligand to a natural photosensitizer derived from Chinese herb.The photophysical and photochemical properties were investigated through UV-visible and fluorescence spectrophotometer,and the photodynamic activity was evaluated with MTT assay.RESULTS An endogenous enzyme-NQO1 activated hypericin was prepared and fully characterized with various spectroscopic methods.The electronic absorption was almost the same with the free hypericin,indicating the introducing of the ligand to hypericin has little effect to its ground state,while there is almost no detected fluorescence and reactive oxygen species(ROS)generation in PBS solution indicating the introducing of the ligand can effectively quench the fluorescence emission and ROS generation.The in vitro study showed that both compounds have almost no dark toxicity,but they are highlyphotocytoxic with an IC50 less than 1μmol·L-1 against A549 cell lines indicating the modified compound can be activated in the intracellular environment.CONCLUSION A simple and efficient hypericin-based activated photosensitizer was prepared.The ROS generation was quenched in PBS solution and it would be activated inside A549 cell lines.It may be served as apromising tumor selective fluorescent probe and photosensitizer for targeted photodynamic therapy.
基金supported by National Natural Science Foundation of China(81402946)Initializing Fund of Xuzhou Medical University of China(D2014017 and D2014010)Natural Science Research Grant of Higher Education of Jiangsu Province of China(14KJD310002)
文摘OBJECTIVE To explore the effect of connexin(Cx)40-formed gap junctional intercellular communication(GJIC)on Photofrin-photodynamic therapy(PDT)phototoxicity in Cx40-transfected He La cells and its potential mechanisms.METHODS He La cell line stably transfected to express Cx40 was seeded at high and low cell density,respectively,to assess in vitro photosensitivity using CCK8 assay.Western blot assay was performed to detect the expression of Cx40.The intracellular ROS and Ca^(2+) concentrations were determined using flow cytometer.4-HNE and ceramide were measured using ELISA assay.RESULTS Cx40-composed GJ formation at high density enhances the phototoxicity of PhotofrinPDT.When the Cx40 is not expressed or Cx40 channels are blocked,the phototoxicity in high-density cultures substantially reduces,indicating that the enhanced PDT phototoxicity at high density is mediated by Cx40-composed GJIC.The GJIC-mediated increase in PDT phototoxicity was associated with ROS and calcium-mediated stress signaling pathways.CONCLUSION The work uniquely presents the ability of Cx40-composed GJIC to enhance the sensitivity of malignant cells to PDT,and indicates that maintenance or increase of Cx40-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency.
基金The project supported by Health and Medical Research Fund(1100502,13120442and 12110442)the general research fund(GRF)grant from Hong Kong research grant committee(476912)
文摘Malignant tumors and infectious diseases are two main threats to human beings.Photodynamic therapy(PDT)is an effective approach to treat malignancies and infections through the generation of reactive oxygen species(ROS)of a non-toxic photodynamic drug(photosensitizing agent)upon light irradiation.PDT shows promising in treating areas where light can reach,for example,skin and cavities.To treat the problems on deep tissues,much evidence has accumulated in recent years suggesting that sonodynamic therapy(SDT),which eradicates malignant or infectious cells by ROS produced from the interaction of ultrasound energy and sonodynamic drug(sonosensitizing agent),has potential in treating diseases in deep tissues because ultrasound energy has deeper tissue penetration than light energy.Natural products are a valuable source for developing novel drugs.In recent years,we are focusing on developing novel and naturally occurring photodynamic and sonodynamic agents.We have found some active components from natural products,for example,curcumin and hypocrellin,have not only photodynamic activity and also sonodynamic activity in killing bacterial and tumor cells.This talk will briefly introduce two new technologies including photodynamic and sonodynamic therapy,and highlight the recent development in photodynamic and sonodynamic drugs from natural products or traditional Chinese medicines.Chemical modifications of the active compounds have also been attempted to achieve better results.
文摘Corrole,a representative branch of porphyrin,has recently gained popularity.These molecules,viewed as ring‑contracted porphyrinoids containing direct pyrrole‑pyrrole linkages due to the absence of a meso‑carbon atom,exhibit significant photo‑physicochemical properties that make them attractive for various applications.Herein,this review comprehensively discusses the remarkable properties of corrole complexes,as well as related structures and chelation properties.It further explores the biological applications of corrole complexes for in vivo imaging and anticancer therapy.Additionally,it addresses common research bottlenecks and challenges,providing insights into future potential applications in disease diagnosis and treatment.Generally,this review aims to illuminate the significance of corrole complexes and their promising biological applications.
文摘OBJECTIVE Hypericin,a powerful naturally photosensitizer in photodynamic therapy(PDT),is suitable for treating skin diseases involving excess capillary proliferation.In the present study,we aimed to evaluate the skin penetrability of a topically applied hypericin,expecting reducing the risk of prolonged skin photosensitivity,which often occurs after systemic administration.METHODS The Franz diffusion cell assay was performed to evaluate different penetration enhancers.In vivo studies,fluorescence microscopy was performed to examine the distribution of hypericin in the skin,macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment.Immunohistochemistry was used to determine the expression of PECAM-1 in the treated skin.RESULTS 5% menthol facilitated hypericin penetrate the skin of nude mice most.The results of in vivo assays revealed that hypericin penetrated nude mice skin,spread to the dermis,and resulted in obvious photosensitivity reaction on the dermal capillaries.Moreover,skin injured by the photosensitive reaction induced by hypericin was replaced by normal skin 7 d after hypericin-PDT treatment.CONCLUSION Topical hypericin could penetrate nude mouse skin well and be great potential in PDT treatment of skin diseases.
