1.A novel dual-targeting strategy of nanobody-driven protein corona modulation for glioma therapy.
Yupei ZHANG ; Shugang QIN ; Tingting SONG ; Zhiying HUANG ; Zekai LV ; Yang ZHAO ; Xiangyu JIAO ; Min SUN ; Yinghan ZHANG ; Guang XIE ; Yuting CHEN ; Xuli RUAN ; Ruyue LIU ; Haixing SHI ; Chunli YANG ; Siyu ZHAO ; Zhongshan HE ; Hai HUANG ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2025;15(9):4917-4931
Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.
2.The assessment of hepatic hemodynamic characteristics in cirrhotic patients with splenectomy based on iodine map of dual-source CT
Yongyue ZHU ; Zhou ZHOU ; Chengli ZHAO ; Yinghan SUN ; Cong ZHOU ; Daoqing WANG
Journal of Practical Radiology 2024;40(2):302-305
Objective To investigate the hepatic hemodynamic characteristics of cirrhotic patients with splenectomy using iodine map of dual-source computed tomography(DSCT).Methods Twenty-four cirrhotic patients with splenectomy were selected as a study group,41 cirrhotic patients without splenectomy as a cirrhosis group and other 32 patients with normal liver as a control group.The iodine concentration(IC)in hepatic arterial and venous phases was measured on the iodine map,and the arterial iodine fraction(AIF)and portal venous iodine concentration(PVIC)were calculated.Receiver operating characteristic(ROC)curves were plotted and the area under the curve(AUC)was recorded to evaluate the diagnostic efficacy of each parameter using the DeLong test.Results IC in arterial phase and AIF were significantly higher,and IC in venous phase and PVIC were significantly lower in study group(P<0.05).The AUC values of the four parameters between study group and cirrhosis group were 0.735,0.992,0.943,and 0.994,respectively.Conclusion DSCT iodine map is helpful for clinical quantitative assessment of hepatic hemodynamic characteristics in cirrhotic patients with splenectomy,and the PVIC has optimal independent diagnostic performance.

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