High-intensity focused ultrasound(HIFU),with inherent advantages of improved ultrasonic depth and low off-target damage,holds the promising capability for glioma treatment,but the relatively long therapeutic time and ...High-intensity focused ultrasound(HIFU),with inherent advantages of improved ultrasonic depth and low off-target damage,holds the promising capability for glioma treatment,but the relatively long therapeutic time and potential physical complications may hamper its clinical application.Herein,a bovine serum albumin(BSA)-based nanoplatform with in situ growth of MnO_(2) was synthesized,and Protoporphyrin IX(PpIX)was further anchored to obtain a versatile PpIX@MnO_(2)@BSA nanoplatform(denoted as BMP).By employing HIFU as the exogenous irradiation source,a high-efficacy sonodynamic therapy(SDT)is developed,in which the excited BMP enables the production of tumoricidal reactive oxygen species(ROS).The inherent tumor microenvironment(TME)-responsive property of MnO_(2) endows BMP with specific T1-weighted magnetic resonance imaging(MRI)by releasing Mn2+,and the simultaneously generated O_(2) facilitates hypoxia alleviation as well as ^(1)O_(2) generation.Compared with HIFU therapy alone,suppression of glioma growth and improved survival benefits are achieved through the designed TMEresponsive nanocomposite under HIFU exposure.The high-efficacy SDT strategy combining BMP and HIFU demonstrated favorable TME-responsive T1-weighted MRI,hypoxic environment alleviation,and anti-tumor capability,providing a perspective paradigm for MRI-guided glioma treatment.展开更多
Many scientific efforts have been made to penetrate the blood-brain barrier and target glioblastoma cells,but the outcomes have been limited.More attention should be given to local inhibition of recurrence after gliob...Many scientific efforts have been made to penetrate the blood-brain barrier and target glioblastoma cells,but the outcomes have been limited.More attention should be given to local inhibition of recurrence after glioblastoma resection to meet real medical needs.A biodegradable wafer containing the chemotherapeutics carmustine(1,3-bis(2-chloroethyl)-1-nitrosourea,BCNU)was the only local drug delivery system approved for clinical glioblastoma treatment,but with a prolonged survival time of only two months and frequent side effects.In this study,to improve the sustained release and prolonged therapeutic effect of drugs for inhibiting tumor recurrence after tumor resection,both free BCNU and BCNU-poly(lactic-co-glycolic acid)(the ratio of lactic acid groups to glycolic acid groups is 75/25)nanoparticles were simultaneously loaded into natural extracellular matrix hydrogel from pigskin to prepare BCNU gels.The hydrogel was injected into the resection cavity of a glioblastoma tumor immediately after tumor removal in a fully characterized resection rat model.Free drugs were released instantly to kill the residual tumor cells,while drugs in nanoparticles were continuously released to achieve a continuous and effective inhibition of the residual tumor cells for 30 days.These combined actions effectively restricted tumor growth in rats.Thus,this strategy of local drug implantation and delivery may provide a reliable method to inhibit the recurrence of glioblastoma after tumor resection in vivo.展开更多
基金supported by the Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)ZJ Lab,Shanghai Center for Brain Inspired Technology,and the Youth Program of National Natural Science Foundation of China(No.81901697).
文摘High-intensity focused ultrasound(HIFU),with inherent advantages of improved ultrasonic depth and low off-target damage,holds the promising capability for glioma treatment,but the relatively long therapeutic time and potential physical complications may hamper its clinical application.Herein,a bovine serum albumin(BSA)-based nanoplatform with in situ growth of MnO_(2) was synthesized,and Protoporphyrin IX(PpIX)was further anchored to obtain a versatile PpIX@MnO_(2)@BSA nanoplatform(denoted as BMP).By employing HIFU as the exogenous irradiation source,a high-efficacy sonodynamic therapy(SDT)is developed,in which the excited BMP enables the production of tumoricidal reactive oxygen species(ROS).The inherent tumor microenvironment(TME)-responsive property of MnO_(2) endows BMP with specific T1-weighted magnetic resonance imaging(MRI)by releasing Mn2+,and the simultaneously generated O_(2) facilitates hypoxia alleviation as well as ^(1)O_(2) generation.Compared with HIFU therapy alone,suppression of glioma growth and improved survival benefits are achieved through the designed TMEresponsive nanocomposite under HIFU exposure.The high-efficacy SDT strategy combining BMP and HIFU demonstrated favorable TME-responsive T1-weighted MRI,hypoxic environment alleviation,and anti-tumor capability,providing a perspective paradigm for MRI-guided glioma treatment.
基金supported by the National Natural Science Foundation of China(Grant Nos.82074277,8177391)the Basic Research Cooperation Project of Beijing,Tianjin,Hebei from the Natural Science Foundation of Tianjin(Grant Nos.20JCZXJC00070 and J200018)the Young Elite Scientists Sponsorship Program of Tianjin(Grant No.TJSQNTJ-2017-14).
文摘Many scientific efforts have been made to penetrate the blood-brain barrier and target glioblastoma cells,but the outcomes have been limited.More attention should be given to local inhibition of recurrence after glioblastoma resection to meet real medical needs.A biodegradable wafer containing the chemotherapeutics carmustine(1,3-bis(2-chloroethyl)-1-nitrosourea,BCNU)was the only local drug delivery system approved for clinical glioblastoma treatment,but with a prolonged survival time of only two months and frequent side effects.In this study,to improve the sustained release and prolonged therapeutic effect of drugs for inhibiting tumor recurrence after tumor resection,both free BCNU and BCNU-poly(lactic-co-glycolic acid)(the ratio of lactic acid groups to glycolic acid groups is 75/25)nanoparticles were simultaneously loaded into natural extracellular matrix hydrogel from pigskin to prepare BCNU gels.The hydrogel was injected into the resection cavity of a glioblastoma tumor immediately after tumor removal in a fully characterized resection rat model.Free drugs were released instantly to kill the residual tumor cells,while drugs in nanoparticles were continuously released to achieve a continuous and effective inhibition of the residual tumor cells for 30 days.These combined actions effectively restricted tumor growth in rats.Thus,this strategy of local drug implantation and delivery may provide a reliable method to inhibit the recurrence of glioblastoma after tumor resection in vivo.
