Invasive grade III and IV maliguant gliomas remain difficult to treat with a typical survival time post-diagnosis hovering around 16 months with only minor extension thereof seen in the past decade,whereas some improv...Invasive grade III and IV maliguant gliomas remain difficult to treat with a typical survival time post-diagnosis hovering around 16 months with only minor extension thereof seen in the past decade,whereas some improvements have been obtained towards five-year survival rates for which completeness of resection is a prerequisite.Optical techniques such as fluorescence guided resection(FGR)and photodynamic therapy(PDT)are promising adjuvant techniques to in-crease the tumor volume reduction fraction.PDT has been used in combination with surgical resection or alternatively as standalone treat ment strategy with some sucoess in extending the median survival time of patients compared to surgery alone and the current standard of care.This document reviews the outcome of past clinical trials and highlights the general shift in PDT therapeutic approaches.It also looks at the current approaches for interstitial PDT and research options into increasing PDT's glioma treatment fficacy through exploiting both physical and biological based approaches to maximize PDT selectivity and therapeutic index,particularly in brain adjacent to tumor(BAT).Potential reasons for failing to demonstrate a significant survival advantage in prior PDT clinical trials will become evident in light of the improved understanding of glioma biology and PDT dosimetry.展开更多
We welcome the readers to Part Ⅱ of the special issue on Enhanced Photodynamic Therapy(PDT),an issue dedicated to highlighting the latest developments in both fundamental mechanisms and clinical applications for enha...We welcome the readers to Part Ⅱ of the special issue on Enhanced Photodynamic Therapy(PDT),an issue dedicated to highlighting the latest developments in both fundamental mechanisms and clinical applications for enhanced PDT.Therst part of this special issue was published in July 2022 as Issue 4 of Volume 15,andve research articles were included.1 It is really exciting that we have an enthusiastic response from our colleagues that continuously contributed eight articles to produce Part II.We believe these two special issues will provide a better understanding of enhanced PDT.展开更多
Photodynamic therapy(PDT)utilizes photosensi-tizer(PS)together with irradiation light of specific wavelength interacting with oxygen to generate cytotoxic reactive oxygen species,which has been approved for the treatm...Photodynamic therapy(PDT)utilizes photosensi-tizer(PS)together with irradiation light of specific wavelength interacting with oxygen to generate cytotoxic reactive oxygen species,which has been approved for the treatment of several maligr nant and non-malignant pathologies.Most recently,en-hanced PDT has been achieved by using novel nano-PSs,1 new light sources,2 oxygen supply,and synergistic therapy.展开更多
Photodynamic therapy(PDT)utilizes light and photosensitizer(PS)to generate reactive oxygen species(ROS)to kill cancer cells,presenting a promising strategy as an anti-cancer treatment.However,the low hydrophilicity an...Photodynamic therapy(PDT)utilizes light and photosensitizer(PS)to generate reactive oxygen species(ROS)to kill cancer cells,presenting a promising strategy as an anti-cancer treatment.However,the low hydrophilicity and poor targeting of currently used PSs,as well as the abnormal tumor microenvironment(TME),limit the clinical application of PDT.Herein,nontoxic liposomes with the ability to incorporate both hydrophilic and hydrophobic PS are used as the nanocarrier to co-load Hemoporfin,L-buthionine sulfoximine(BSO),and catalase(CAT)to obtain BSO/CAT@Liposomes-Hemoporfin nanoparticles(BCHL NPs),which could be used to remodel the TME and to enhance Hemoporfin-mediated PDT efficacy.BCHL NPs exhibit a long blood circulation time and can accumulate in the tumor.BSO can reduce the cytosolic concentration of glutathione(GSH),a natural scavenger of ROS.CAT catalyzes the endogenously overexpressed H_(2)O_(2)in the tumor site into H_(2)O and O_(2),thus relieving tumor hypoxia and enhancing ROS generation.Upon irradiation,the synergetic effects of reduced GSH synthesis by BSO and relieved hypoxia by CAT were observed in 4T1 tumor-bearing mouse model.Compared to the tumor treated by free Hemoporfin,BCHL NPs-mediated PDT resulted in 1.25-fold higher inhibition of tumor growth due to the enhanced ROS generation.The present study provides insight into the design of efficient strategies for enhanced clinic Hemoporfin-mediated PDT efficiency.展开更多
基金supported by the Ontario Ministry of Health and Long-term Care and a grant from the Canadian Institute of Health Research grant number MOP-93567.
文摘Invasive grade III and IV maliguant gliomas remain difficult to treat with a typical survival time post-diagnosis hovering around 16 months with only minor extension thereof seen in the past decade,whereas some improvements have been obtained towards five-year survival rates for which completeness of resection is a prerequisite.Optical techniques such as fluorescence guided resection(FGR)and photodynamic therapy(PDT)are promising adjuvant techniques to in-crease the tumor volume reduction fraction.PDT has been used in combination with surgical resection or alternatively as standalone treat ment strategy with some sucoess in extending the median survival time of patients compared to surgery alone and the current standard of care.This document reviews the outcome of past clinical trials and highlights the general shift in PDT therapeutic approaches.It also looks at the current approaches for interstitial PDT and research options into increasing PDT's glioma treatment fficacy through exploiting both physical and biological based approaches to maximize PDT selectivity and therapeutic index,particularly in brain adjacent to tumor(BAT).Potential reasons for failing to demonstrate a significant survival advantage in prior PDT clinical trials will become evident in light of the improved understanding of glioma biology and PDT dosimetry.
文摘We welcome the readers to Part Ⅱ of the special issue on Enhanced Photodynamic Therapy(PDT),an issue dedicated to highlighting the latest developments in both fundamental mechanisms and clinical applications for enhanced PDT.Therst part of this special issue was published in July 2022 as Issue 4 of Volume 15,andve research articles were included.1 It is really exciting that we have an enthusiastic response from our colleagues that continuously contributed eight articles to produce Part II.We believe these two special issues will provide a better understanding of enhanced PDT.
文摘Photodynamic therapy(PDT)utilizes photosensi-tizer(PS)together with irradiation light of specific wavelength interacting with oxygen to generate cytotoxic reactive oxygen species,which has been approved for the treatment of several maligr nant and non-malignant pathologies.Most recently,en-hanced PDT has been achieved by using novel nano-PSs,1 new light sources,2 oxygen supply,and synergistic therapy.
基金National Natural Science Foundation of China,Grant/Award Numbers:62227823,61935004。
文摘Photodynamic therapy(PDT)utilizes light and photosensitizer(PS)to generate reactive oxygen species(ROS)to kill cancer cells,presenting a promising strategy as an anti-cancer treatment.However,the low hydrophilicity and poor targeting of currently used PSs,as well as the abnormal tumor microenvironment(TME),limit the clinical application of PDT.Herein,nontoxic liposomes with the ability to incorporate both hydrophilic and hydrophobic PS are used as the nanocarrier to co-load Hemoporfin,L-buthionine sulfoximine(BSO),and catalase(CAT)to obtain BSO/CAT@Liposomes-Hemoporfin nanoparticles(BCHL NPs),which could be used to remodel the TME and to enhance Hemoporfin-mediated PDT efficacy.BCHL NPs exhibit a long blood circulation time and can accumulate in the tumor.BSO can reduce the cytosolic concentration of glutathione(GSH),a natural scavenger of ROS.CAT catalyzes the endogenously overexpressed H_(2)O_(2)in the tumor site into H_(2)O and O_(2),thus relieving tumor hypoxia and enhancing ROS generation.Upon irradiation,the synergetic effects of reduced GSH synthesis by BSO and relieved hypoxia by CAT were observed in 4T1 tumor-bearing mouse model.Compared to the tumor treated by free Hemoporfin,BCHL NPs-mediated PDT resulted in 1.25-fold higher inhibition of tumor growth due to the enhanced ROS generation.The present study provides insight into the design of efficient strategies for enhanced clinic Hemoporfin-mediated PDT efficiency.
