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.Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine.
Xing DUAN ; Yi ZHANG ; Mengran GUO ; Na FAN ; Kepan CHEN ; Shugang QIN ; Wen XIAO ; Qian ZHENG ; Hai HUANG ; Xiawei WEI ; Yuquan WEI ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2023;13(3):942-954
The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.
3.Effect of Short-term Complications After D2 Radical Gastrectomy on Long-term Survival Rate of Gastric Cancer Patients
Penghang LIN ; Chunlin LIN ; Qin WANG ; Ruofan HE ; Hui CHEN ; Yongjian HUANG ; Shugang YANG ; Jianxin YE ; Guangwei ZHU
Cancer Research on Prevention and Treatment 2021;48(6):625-630
Objective To investigate the effect of short-term complications after D2 radical gastrectomy on long-term survival rate of gastric cancer patients. Methods A retrospective case-control study was conducted on 421 patients with gastric cancer who underwent D2 radical gastrectomy. According to the short-term postoperative complications, they were divided into experimental group (complication group,
4.Prenatal exposure to lipopolysaccharide results in lipid metabolism and FAT/CD36 expression in mice offspring
Shugang QIN ; Xin CHEN ; Yi JIA ; Jianzhi ZHOU ; Min SU ; Xiaohui LI
Chinese Pharmacological Bulletin 2016;32(8):1080-1085
Aim To explore the effect of prenatal expo-sure to lipopolysaccharide ( LPS ) on lipid metabolism in mice offspring from the starting point of FAT/CD36 expression.Methods 8-week old C57 mice mated 2∶1, then they were caged separately , marked as preg-nancy 0 d.The pregnant mice were given single intrap-eritoneal injection of 75 μg? kg -1 LPS, and the con-trol received injections of 0.2 mL saline .The perirenal adipose of female mice and epididymis adipose of male mice were collected in 4 w,8 w,12 w,respectively. The weight of visceral adipose tissue and the free fatty acid( FFA) and triglyceride ( TG) of adipose tissue and FAT/CD36 of offspring mice were quantitated .Results The body weight of offspring of LPS group was also significantly higher than that of NS group , and LPS group offspring displayed increased adipose tissue wet weights , the expression of TG and FFA was increased in LPS group compared with NS .Especially , prenatal exposure to inflammatory stimulation resulted in marked increase of FAT/CD36 and abnormal adipocyte development .Conclusions Inflammation induced by prenatal exposure to LPS results in increased body weight , adipose coefficient and FAT/CD36 that might develop into obesity in adult mice .These results are relevant in that anomalous local adipose tissue and FAT/CD36 regulation may be an important mechanism underlying obesity .

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