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.

Objective To explore the changes of serum tryptase(TPS)and interleuk-6 (IL-6)levels before and after TACE treatment in patients with hepatocellular carcinoma (HCC).Methods ELISA was used to detect the serum TPS and IL-6 levels in 5 1 patients with HCC 1 day before and 1 day,1 week and 1 month after TACE.30 healthy people were enrolled as a control group.Results Serum TPS and IL-6 levels in observation group before TACE were higher than those in control group (P＜0.05),and serum TPS level in the observation group was positively correlated with serum IL-6 level (P＜0.05)before TACE.Serum TPS and IL-6 levels in the response group one month after TACE were lower than those one day before TACE (P＜0.05),while compared with those one day before TACE ,the non-response group increased slightly and non significance was showed(P＞0.05).Conclusion Serum TPS and IL-6 levels are closely related to the response of HCC to TACE treatment,thus these may be used to evaluate the efficacy of TACE in treatment of HCC.

Objective To evaluate the relationship between hippocampal cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway and cognitive dysfunction in rats with chronic pathological pain.Methods Thirty-two healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 3 groups using a random number table:control group(group C,n=8),sham operation group(group S,n=8)and chronic pathological pain group(group CP,n=16).Chronic pathological pain model was established by injecting cobra venom 0.4 mg(4 μl)into the sheath of the infraorbital nerve.The mechanical pain threshold was measured at 3 days before establishment of the model(baseline)and 4 days and 1,2,3,4 and 8 weeks after establishment of the model.Morris water maze test was performed to evaluate the spatial learning and memory abilities at 5 and 9 weeks after establishment of the model.Eight rats were sacrificed at 5 and 9 weeks after establishment of the model in CP group,and rats were sacrificed after the end of Morris water maze test at 9 weeks after establishment of the model in C and S groups.The hippocampi were isolated for determination of the expression of phosphorylated CREB and BDNF in the hippocampal tissues using Western blot.Results Compared with group C,the mechanical pain threshold was significantly decreased at each time point after establishment of the model,the escape latency was prolonged at 5 and 9 weeks after establishment of the model,the rate of time of staying at the target quadrant was decreased,the frequency of crossing the original platform was decreased,and the expression of phosphorylated CREB and BDNF was down-regulated at 9 weeks after establishment of the model in group CP(P<0.05),and no significant change was found in the parameters mentioned above in group S(P>0.05).Conclusion The mechanism underlying cognitive dysfunction may be related to inhibited activation of CREB/BDNF signaling pathway in the hippocampus of rats with chronic pathological pain.

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus formation in the main vasculature is extremely poor. Sorafenib combined with transarterial chemoembolization is a novel treatment approach for advanced HCC. In this study, we report two HCC patients with inferior vena cava tumor thrombus who underwent the combination treatment. The overall survival times for these two patients were 44 months and 35 months, respectively. Our report suggests that sorafenib combined with transarterial chemoembolization may be a viable choice for patients with advanced HCC even with inferior vena cava tumor thrombus. Further studies are required to verify the efficacy and safety of this combination therapy for patients with advanced HCC with inferior vena cava tumor thrombus.
Carcinoma, Hepatocellular ; drug therapy ; Catheterization, Peripheral ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Hepatic Artery ; Humans ; Liver Neoplasms ; drug therapy ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Prognosis ; Thrombosis ; Vena Cava, Inferior