Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strong...Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.展开更多
The recent interest in precision medicine among interventionists has led to the establishment of the concept of precision interventional radiology(PIR).This concept focuses not only on the accuracy of interventional o...The recent interest in precision medicine among interventionists has led to the establishment of the concept of precision interventional radiology(PIR).This concept focuses not only on the accuracy of interventional operations using traditional image-guided techniques,but also on the comprehensive evaluation of diseases.The invisible features extracted from CT,MRI,or US improve the accuracy and specificity of diagnosis.The integration of multi-omics and molecule imaging provides more information for interventional operations.The development and application of drugs,embolic materials,and devices broaden the concept of PIR.Integrating medicine and engineering brings new image-guided techniques that increase the efficacy of interventional operations while reducing the complications of interventional treatment.In all,PIR,an important part of precision medicine,emphasizing the whole disease management process,including precision diagnosis,comprehensive evaluation,and interventional therapy,maximizes the benefits of patients with limited damage.展开更多
The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous poly...The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.展开更多
diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance im...diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging(MRI)-guided cancer chemo-photothermal therapy.Superparamagnetic iron oxide(SPIO)-loaded MPDA NPs(MPDA@SPIO)was firstly prepared,followed by modifying with a targeted molecule of sialic acid(SA)and chelating with Fe^(3+)(SA-MPDA@SPIO/Fe^(3+) NPs).After that,doxorubicin(DOX)-loaded SA-MPDA@SPIO/Fe^(3+) NPs(SA-MPDA@SPIO/DOX/Fe^(3+))was prepared for tumor theranostics.The prepared SAPEG-MPDA@SPIO/Fe^(3+) NPs were water-dispersible and biocompatible as evidenced by MTT assay.In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability,with relaxivity of being r1=4.29 mM1s1 and r2=105.53 mM1s1,respectively.SAPEG-MPDA@SPIO/Fe^(3+) NPs could effectively encapsulate the DOX,showing dual pH-and thermal-triggered drug release behavior.In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe^(3+) NPs could effectively target to the hepatic tumor tissue,which was possibly due to the specific interaction between SA and the overexpressed E-selectin.This behavior also endowed SA-MPDA@SPIO/DOX/Fe^(3+)NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification.In addition,SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs displayed a superior therapeutic effect,which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy.These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs is an effective targeted nanoplatform for tumor theranostics,having potential value in the effective treatment of hepatic cancer.展开更多
Dear Editor,The application of immune checkpoint inhibitors(ICIs),anti-tumor immunotherapy unleashing the host immune system to eradicate tumor cells,has revolutionized the treatment of various advanced cancers and sh...Dear Editor,The application of immune checkpoint inhibitors(ICIs),anti-tumor immunotherapy unleashing the host immune system to eradicate tumor cells,has revolutionized the treatment of various advanced cancers and showed remarkable anti-tumor effects[1].However,emphasis must be placed on fatal immune-related adverse events(irAEs),especially some fulminant irAEs like ICI-related cardiovascular AEs[2,3].However,due to the low rate of cardiovascular AEs,little is known about the effective methods for evaluating the risk of catastrophic cardiac events in ICI-associated myocarditis and its management[4,5].展开更多
Neurofibromatosis(NF)is a genetic disease in which the lungs are rarely involved.However,in NF cases with lung involvement,chest computed tomography may show bilateral basal reticulations,apical bullae,and cysts witho...Neurofibromatosis(NF)is a genetic disease in which the lungs are rarely involved.However,in NF cases with lung involvement,chest computed tomography may show bilateral basal reticulations,apical bullae,and cysts without bronchiectasis.Herein,we report a patient diagnosed with NF on the basis of the results of genetic testing who presented with early-onset wet cough and bronchiectasis.Considering the differential diagnosis of bronchiectasis combined with his early-onset wet cough,sinusitis,and sperm quality decline,we considered the possibility of primary ciliary dyskinesia(PCD).Further electron microscopy analysis of cilia and identification of homozygous mutations in the RSPH4A gene confirmed the diagnosis of PCD.Therefore,for patients with NF,when an image change exists in the lungs that does not correspond to NF,the possibility of other diagnoses,including PCD,must be considered.展开更多
The size and density of Ag nanoparticles on n-layer MoS2 exhibit thickness- dependent behavior. The size and density of these particles increased and decreased, respectively, with increasing layer number （n） of n-la...The size and density of Ag nanoparticles on n-layer MoS2 exhibit thickness- dependent behavior. The size and density of these particles increased and decreased, respectively, with increasing layer number （n） of n-layer MoS2. Furthermore, the surface-enhanced Raman scattering （SERS） of Ag on this substrate was observed. The enhancement factor of this scattering varied with the thickness of MoS2. The mechanisms governing the aforementioned thickness dependences are proposed and discussed.展开更多
基金supported by the Key R&D Program of Lishui City(2021ZDYF12,2022ZDYF07,2023zdyf14)Natural Science Foundation of China(82072026,82072025 and 82272090)+1 种基金Zhejiang Provincial Natural Science Foundation(LY23H180003,LQ22H180010)Provincial and Ministerial Joint Construction of Key Projects(WKJ-ZJ-2317).
文摘Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.
基金supported by National Key Research and Development projects intergovernmental cooperation in science and technology of China(2018YFE0126900)National Natural Science Foundation of China(grant number 81803778)Zhejiang Provincial Natural Science Foundation(LQ20H160055)。
文摘The recent interest in precision medicine among interventionists has led to the establishment of the concept of precision interventional radiology(PIR).This concept focuses not only on the accuracy of interventional operations using traditional image-guided techniques,but also on the comprehensive evaluation of diseases.The invisible features extracted from CT,MRI,or US improve the accuracy and specificity of diagnosis.The integration of multi-omics and molecule imaging provides more information for interventional operations.The development and application of drugs,embolic materials,and devices broaden the concept of PIR.Integrating medicine and engineering brings new image-guided techniques that increase the efficacy of interventional operations while reducing the complications of interventional treatment.In all,PIR,an important part of precision medicine,emphasizing the whole disease management process,including precision diagnosis,comprehensive evaluation,and interventional therapy,maximizes the benefits of patients with limited damage.
基金supported by the National Key Research and Development projects intergovernmental cooperation in science and technology of China(2018YFE0126900)National Natural Science Foundation of China(82072025 and82072026)+2 种基金Zhejiang Provincial Natural Science Foundation(LQ21H180003)Key R&D Program of Lishui City(2021ZDYF12)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(2022RC088)。
文摘The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.
基金supported by Institute of Nanomaterials and Nanotechnology,Lishui Hospital of Zhejiang UniversityPostdoctoral Foundation of ZheJiang province+2 种基金National Key Research and Development projects intergovernmental cooperation in science and technology of China(2018YFE0126900)Zhejiang Provincial Natural Science Foundation(LY15H030010,LY20H180016,Q21H180011)The Key R&D Program of Lishui City(2019ZDYF17).
文摘diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging(MRI)-guided cancer chemo-photothermal therapy.Superparamagnetic iron oxide(SPIO)-loaded MPDA NPs(MPDA@SPIO)was firstly prepared,followed by modifying with a targeted molecule of sialic acid(SA)and chelating with Fe^(3+)(SA-MPDA@SPIO/Fe^(3+) NPs).After that,doxorubicin(DOX)-loaded SA-MPDA@SPIO/Fe^(3+) NPs(SA-MPDA@SPIO/DOX/Fe^(3+))was prepared for tumor theranostics.The prepared SAPEG-MPDA@SPIO/Fe^(3+) NPs were water-dispersible and biocompatible as evidenced by MTT assay.In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability,with relaxivity of being r1=4.29 mM1s1 and r2=105.53 mM1s1,respectively.SAPEG-MPDA@SPIO/Fe^(3+) NPs could effectively encapsulate the DOX,showing dual pH-and thermal-triggered drug release behavior.In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe^(3+) NPs could effectively target to the hepatic tumor tissue,which was possibly due to the specific interaction between SA and the overexpressed E-selectin.This behavior also endowed SA-MPDA@SPIO/DOX/Fe^(3+)NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification.In addition,SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs displayed a superior therapeutic effect,which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy.These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs is an effective targeted nanoplatform for tumor theranostics,having potential value in the effective treatment of hepatic cancer.
基金the Youth Program of National Natural Science Foundation of China(to YX)(82003309)the National Key Research and Development Program of China(to WW)(2016YFC0905102)CAMS Innovation Fund for Medical Sciences(to WW)(CIFMS)(2017-I2M-2-002).
文摘Dear Editor,The application of immune checkpoint inhibitors(ICIs),anti-tumor immunotherapy unleashing the host immune system to eradicate tumor cells,has revolutionized the treatment of various advanced cancers and showed remarkable anti-tumor effects[1].However,emphasis must be placed on fatal immune-related adverse events(irAEs),especially some fulminant irAEs like ICI-related cardiovascular AEs[2,3].However,due to the low rate of cardiovascular AEs,little is known about the effective methods for evaluating the risk of catastrophic cardiac events in ICI-associated myocarditis and its management[4,5].
基金supported by the National Key Research and Development Program of China(No.2016YFC0901502)CAMS Innovation Fund for Medical Sciences(Nos.CIFMS-2018-I2M-1-003,CIFMS-2017-12M-2-001,CIFMS-2020-I2M-C&T-B-002,and CIFMS-2016-I2M-1-002).
文摘Neurofibromatosis(NF)is a genetic disease in which the lungs are rarely involved.However,in NF cases with lung involvement,chest computed tomography may show bilateral basal reticulations,apical bullae,and cysts without bronchiectasis.Herein,we report a patient diagnosed with NF on the basis of the results of genetic testing who presented with early-onset wet cough and bronchiectasis.Considering the differential diagnosis of bronchiectasis combined with his early-onset wet cough,sinusitis,and sperm quality decline,we considered the possibility of primary ciliary dyskinesia(PCD).Further electron microscopy analysis of cilia and identification of homozygous mutations in the RSPH4A gene confirmed the diagnosis of PCD.Therefore,for patients with NF,when an image change exists in the lungs that does not correspond to NF,the possibility of other diagnoses,including PCD,must be considered.
文摘The size and density of Ag nanoparticles on n-layer MoS2 exhibit thickness- dependent behavior. The size and density of these particles increased and decreased, respectively, with increasing layer number （n） of n-layer MoS2. Furthermore, the surface-enhanced Raman scattering （SERS） of Ag on this substrate was observed. The enhancement factor of this scattering varied with the thickness of MoS2. The mechanisms governing the aforementioned thickness dependences are proposed and discussed.
