OBJECTIVE To investigate the in vitro lethal effect of photo- dynamic therapy （PDT） using the photosensitizer hematoporphyrin on the human pancreatic cancer cell line Panc-1, the major influencing factors and the me...OBJECTIVE To investigate the in vitro lethal effect of photo- dynamic therapy （PDT） using the photosensitizer hematoporphyrin on the human pancreatic cancer cell line Panc-1, the major influencing factors and the mechanisms of treatment. METHODS Three factors--the time needed for photosensitizer and cell incubation, the photosensitizer concentration （PhoC） and the exposure dose （ExpD）--were examined with different levels of these factors. Optical density （OD） was used as a measure of CCK-8 in the experiment, and was converted to the rate of cell survival. The separate effect of each factor on the photodynamic action was studied, and the interactions were investigated. The effects of different incubation times and PhoC levels on the fluorescence intensity （FI） of the intracellular photosensitizer were determined, and the mechanisms of these factors leading to the therapeutic effects of PDT discussed. RESULTS An increase in the photosensitizer and cell incubation time, an increase of PhoC, and enhancement of the ExpD, produced a corresponding decrease in the rate of Panc-1 cell survival after PDT （P 〈 0.05）. PDT achieved its maximum lethal effects 16 h after starting the incubation, with a PhoC of 10 mg/L and an ExpD of 20 J/cm2; at these levels a synergistic interaction between PhoC and the ExpD occurred, decreasing the cell survival rate （P 〈 0.05）. Neither simple administration of photosensitizer without ExpD （0 J/cm2） or illumination in the absence of PhoC （0 mg/L） affected the rate of cell survival （P 〉 0.05）. With an increase of PhoC and lengthening of the incubation time, the FI of the intracellular photosensitizer accordingly increased （P 〈 0.05）, and attained its maximum value at a PhoC of 10 mg/L and 36 h after the incubation. With an increase of PhoC, the FI of the photosensitizer, hematoporphyrin, in the solution increased progressively at first and then decreased （fluorescence quenching）. CONCLUSION PDT with the photosensitizer hematoporphyrin has clear lethal effects on the human pancreatic cancer cell line Panc-1, but the presence of a photosensitizer and laser irradiation by themselves do not have independent lethal effects. The three influencing factors--the time for photosensitizer and cell incuba- tion, PhoC and ExpD--correlate positively with the PDT response, within certain limits. Beyond these limits, the PDT response does not significantly increase. The main mechanism of the PDT response lies in the effect of these factors on the level of the intracellular photosensitizer and the fluorescence quenching of the photosensitizer. A synergistic effect exists between PhoC and ExpD.展开更多
Photodynamic therapy(PDT)is an effective and promising cancer treatment.PDT directly generates reactive oxygen species(ROS)through photochemical reactions.This oxygen-dependent exogenous ROS has anti-cancer stem cell(...Photodynamic therapy(PDT)is an effective and promising cancer treatment.PDT directly generates reactive oxygen species(ROS)through photochemical reactions.This oxygen-dependent exogenous ROS has anti-cancer stem cell(CSC)effect.In addition,PDT may also increase ROS production by altering metabolism,endoplasmic reticulum stress,or potential of mitochondrial membrane.It is known that the half-life of ROS in PDT is short,with high reactivity and limited diffusion distance.Therefore,the main targeting position of PDT is often the subcellular localization of photosensitizers,which is helpful for us to explain how PDT affects CSC characteristics,including differentiation,selfrenewal,apoptosis,autophagy,and immunogenicity.Broadly speaking,excess ROS will damage the redox system and cause oxidative damage to molecules such as DNA,change mitochondrial permeability,activate unfolded protein response,autophagy,and CSC resting state.Therefore,understanding the molecular mechanism by which ROS affect CSCs is beneficial to improve the efficiency of PDT and prevent tumor recurrence and metastasis.In this article,we review the effects of two types of photochemical reactions on PDT,the metabolic processes,and the biological effects of ROS in different subcellular locations on CSCs.展开更多
Cancer remains a worldwide health problem, being the disease with the highest impact on global health. Even with all the recent technological improvements, recurrence and metastasis still are the main cause of death. ...Cancer remains a worldwide health problem, being the disease with the highest impact on global health. Even with all the recent technological improvements, recurrence and metastasis still are the main cause of death. Since photodynamic therapy (PDT) does not compromise other treatment options and presents reduced long-term morbidity when compared with chemotherapy or radiotherapy, it appears as a promising alternative treatment for controlling malignant diseases. In this review, we set out to perform a broad up-date on PDT in cancer research and treatment, discussing how this approach has been applied and what it could add to breast cancer therapy. We covered topics going from the photochemical mechanisms involved, the different cell death mechanisms being triggered by a myriad of photosensitizers up to the more recent-on-going clinical trials.展开更多
This letter describes semiconducting polymer dots （Pdots） doped with a photosensitizer and modified with a cell penetrating peptide for photodynamic therapy （PDT）. The resulting Pdots exhibited efficient singlet o...This letter describes semiconducting polymer dots （Pdots） doped with a photosensitizer and modified with a cell penetrating peptide for photodynamic therapy （PDT）. The resulting Pdots exhibited efficient singlet oxygen （^1O2） generation mediated by intraparticle energy transfer. Experimental results indicated that the peptide-coated Pdots could promote the cellular uptake and increase the penetration efficiency in vitro, and effectively suppressed tumor growth and enhanced the photodynamic effect in vivo. Our results demonstrate that Pdots with photosensitizer loading and peptide modification hold great promise for cancer therapy.展开更多
基金This work was supported by grants from Guangdong Provincial Natural Science Foundation （06021369） and Guangdong Medical Research Funds （B2006043）.
文摘OBJECTIVE To investigate the in vitro lethal effect of photo- dynamic therapy （PDT） using the photosensitizer hematoporphyrin on the human pancreatic cancer cell line Panc-1, the major influencing factors and the mechanisms of treatment. METHODS Three factors--the time needed for photosensitizer and cell incubation, the photosensitizer concentration （PhoC） and the exposure dose （ExpD）--were examined with different levels of these factors. Optical density （OD） was used as a measure of CCK-8 in the experiment, and was converted to the rate of cell survival. The separate effect of each factor on the photodynamic action was studied, and the interactions were investigated. The effects of different incubation times and PhoC levels on the fluorescence intensity （FI） of the intracellular photosensitizer were determined, and the mechanisms of these factors leading to the therapeutic effects of PDT discussed. RESULTS An increase in the photosensitizer and cell incubation time, an increase of PhoC, and enhancement of the ExpD, produced a corresponding decrease in the rate of Panc-1 cell survival after PDT （P 〈 0.05）. PDT achieved its maximum lethal effects 16 h after starting the incubation, with a PhoC of 10 mg/L and an ExpD of 20 J/cm2; at these levels a synergistic interaction between PhoC and the ExpD occurred, decreasing the cell survival rate （P 〈 0.05）. Neither simple administration of photosensitizer without ExpD （0 J/cm2） or illumination in the absence of PhoC （0 mg/L） affected the rate of cell survival （P 〉 0.05）. With an increase of PhoC and lengthening of the incubation time, the FI of the intracellular photosensitizer accordingly increased （P 〈 0.05）, and attained its maximum value at a PhoC of 10 mg/L and 36 h after the incubation. With an increase of PhoC, the FI of the photosensitizer, hematoporphyrin, in the solution increased progressively at first and then decreased （fluorescence quenching）. CONCLUSION PDT with the photosensitizer hematoporphyrin has clear lethal effects on the human pancreatic cancer cell line Panc-1, but the presence of a photosensitizer and laser irradiation by themselves do not have independent lethal effects. The three influencing factors--the time for photosensitizer and cell incuba- tion, PhoC and ExpD--correlate positively with the PDT response, within certain limits. Beyond these limits, the PDT response does not significantly increase. The main mechanism of the PDT response lies in the effect of these factors on the level of the intracellular photosensitizer and the fluorescence quenching of the photosensitizer. A synergistic effect exists between PhoC and ExpD.
基金Supported by National Natural Science Foundation of China,No.81970569 and No.81773293Natural Science Foundation of Hunan Province,No.2017SK50121.
文摘Photodynamic therapy(PDT)is an effective and promising cancer treatment.PDT directly generates reactive oxygen species(ROS)through photochemical reactions.This oxygen-dependent exogenous ROS has anti-cancer stem cell(CSC)effect.In addition,PDT may also increase ROS production by altering metabolism,endoplasmic reticulum stress,or potential of mitochondrial membrane.It is known that the half-life of ROS in PDT is short,with high reactivity and limited diffusion distance.Therefore,the main targeting position of PDT is often the subcellular localization of photosensitizers,which is helpful for us to explain how PDT affects CSC characteristics,including differentiation,selfrenewal,apoptosis,autophagy,and immunogenicity.Broadly speaking,excess ROS will damage the redox system and cause oxidative damage to molecules such as DNA,change mitochondrial permeability,activate unfolded protein response,autophagy,and CSC resting state.Therefore,understanding the molecular mechanism by which ROS affect CSCs is beneficial to improve the efficiency of PDT and prevent tumor recurrence and metastasis.In this article,we review the effects of two types of photochemical reactions on PDT,the metabolic processes,and the biological effects of ROS in different subcellular locations on CSCs.
基金CAPES, CNPq and FAPESP (2017/03618-6, 2016/04676-7 and 2013/07937-8)
文摘Cancer remains a worldwide health problem, being the disease with the highest impact on global health. Even with all the recent technological improvements, recurrence and metastasis still are the main cause of death. Since photodynamic therapy (PDT) does not compromise other treatment options and presents reduced long-term morbidity when compared with chemotherapy or radiotherapy, it appears as a promising alternative treatment for controlling malignant diseases. In this review, we set out to perform a broad up-date on PDT in cancer research and treatment, discussing how this approach has been applied and what it could add to breast cancer therapy. We covered topics going from the photochemical mechanisms involved, the different cell death mechanisms being triggered by a myriad of photosensitizers up to the more recent-on-going clinical trials.
基金国家自然科学基金(No.21977016)上海市科委基金(No.18430731600,19411970600,19410711000,20430730900,20490740400,21430730100)+1 种基金Foundation of Dongfang Hepatobiliary Surgery Hospital(No.20WQ011)中国博士后基金(No.2020M681126)。
基金financial support from the National Science Foundation of China (No. 81641177)
文摘This letter describes semiconducting polymer dots （Pdots） doped with a photosensitizer and modified with a cell penetrating peptide for photodynamic therapy （PDT）. The resulting Pdots exhibited efficient singlet oxygen （^1O2） generation mediated by intraparticle energy transfer. Experimental results indicated that the peptide-coated Pdots could promote the cellular uptake and increase the penetration efficiency in vitro, and effectively suppressed tumor growth and enhanced the photodynamic effect in vivo. Our results demonstrate that Pdots with photosensitizer loading and peptide modification hold great promise for cancer therapy.
