Necrosis is a form of cell death that occurs only under pathological conditions such as ischemic diseases and traumatic brain injury （TBI）. Non-invasive imaging of the affected tissue is a key component of novel the...Necrosis is a form of cell death that occurs only under pathological conditions such as ischemic diseases and traumatic brain injury （TBI）. Non-invasive imaging of the affected tissue is a key component of novel therapeutic interventions and measurement of treatment responses in patients. Here, we report a bimodal approach for the detection and monitoring of TBI. PEGylated poly（lactic-coglycolic acid） （PLGA） nanoparticles （NPs）, encapsulating both near infrared （NIR） fluorophores and perfluorocarbons （PFCs）, were targeted to necrotic ceils. We used cyanine dyes such as IRDye 800CW, for which we have previously demonstrated specific targeting to intracellular proteins of cells that have lost membrane integrity. Here, we show specific in vivo detection of necrosis by optical imaging and fluorine magnetic resonance imaging （^19F MRI） using newly designed PLGA NP（NIR700 ＋ PFC）-PEG-800CW. Quantitative ex vivo optical imaging and ^19F MR spectroscopy of NIR-PFC content in injured brain regions and in major organs were well correlated. Both modalities allowed the in vivo identification of necrotic brain lesions in a mouse model of TBI, with optical imaging being more sensitive than ^19F MRI. Our results confirm increased blood pool residence time of PLGA NPs coated with a PEG layer and the successful targeting of TBI-damaged tissue. A single PLGA NP containing NIR-PFC enables both rapid qualitative optical monitoring of the TBI state and quantitative 3D information from deeper tissues on the extent of the lesion by MRI. These necrosis-targeting PLGA NPs can potentially be used for clinical diagnosis of brain injuries.展开更多
Dear Editor,Great progress has been made in the clinical use of photodynamic therapy(PDT)for the treatment of patients with superficial tumors[1].However,cancer recurrence and metastasis have limited the application o...Dear Editor,Great progress has been made in the clinical use of photodynamic therapy(PDT)for the treatment of patients with superficial tumors[1].However,cancer recurrence and metastasis have limited the application of PDT in the treatment of solid tumors and advanced cancers.In this context,combining PDT with other complementary immunotherapy regimens may overcome these limitations of PDT[2].展开更多
文摘Necrosis is a form of cell death that occurs only under pathological conditions such as ischemic diseases and traumatic brain injury （TBI）. Non-invasive imaging of the affected tissue is a key component of novel therapeutic interventions and measurement of treatment responses in patients. Here, we report a bimodal approach for the detection and monitoring of TBI. PEGylated poly（lactic-coglycolic acid） （PLGA） nanoparticles （NPs）, encapsulating both near infrared （NIR） fluorophores and perfluorocarbons （PFCs）, were targeted to necrotic ceils. We used cyanine dyes such as IRDye 800CW, for which we have previously demonstrated specific targeting to intracellular proteins of cells that have lost membrane integrity. Here, we show specific in vivo detection of necrosis by optical imaging and fluorine magnetic resonance imaging （^19F MRI） using newly designed PLGA NP（NIR700 ＋ PFC）-PEG-800CW. Quantitative ex vivo optical imaging and ^19F MR spectroscopy of NIR-PFC content in injured brain regions and in major organs were well correlated. Both modalities allowed the in vivo identification of necrotic brain lesions in a mouse model of TBI, with optical imaging being more sensitive than ^19F MRI. Our results confirm increased blood pool residence time of PLGA NPs coated with a PEG layer and the successful targeting of TBI-damaged tissue. A single PLGA NP containing NIR-PFC enables both rapid qualitative optical monitoring of the TBI state and quantitative 3D information from deeper tissues on the extent of the lesion by MRI. These necrosis-targeting PLGA NPs can potentially be used for clinical diagnosis of brain injuries.
基金Yang Hao received finacial support from the China Scholarship and Jilin Province Chinese Postdoctoral International Exchange Program(YJ20220406)Zili Gu,Zhenfeng Yu and Sen Ma received financial support from the China Scholarship Council,and Peter ten Dijke received funding from Cancer Genomics Centre NetherlandsTimo Schomann and Alireza Haghparast received funding from the European Commission,grants H2020-MSCA-RISE CANCER(777682)and H2020-WIDESPREAD-05-2017-Twinning SIMICA(852985).
文摘Dear Editor,Great progress has been made in the clinical use of photodynamic therapy(PDT)for the treatment of patients with superficial tumors[1].However,cancer recurrence and metastasis have limited the application of PDT in the treatment of solid tumors and advanced cancers.In this context,combining PDT with other complementary immunotherapy regimens may overcome these limitations of PDT[2].
