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 synthesize ternary complex of rare earth with L-Leucine and imidazoles and to determine its properties.METHODS:The ternary solid complex was synthesized from the reaction of rare earth chlorate with L-Leucine and imidazoles in the medium of alcohol,and the compositional analysis,properties,mechanism of thermolysis,thermostability and the bacteriostatic action of the ternary complex were studied by chemistry analysis,chemical elements analysis,infrared spectral(IR)analysis,molar conductivity measurement and derivative thermogravimetry(TG-DTG)analysis,bioactivity experiments etc.RESULTS:The constitute structure of the ternary complexes was detected to be electrolyte1∶3type RE(Leu) 3 Im(H 2 O)Cl 3 ?2H 2 O,meanwhile,the thermolysis dynamics,thermostability and the bacteriostatic action against E coli of the ternary complex were established preliminarily.CONCLUSION:The composition and the property of the ternary complexes are stable and which were found to be of good bacteriostatic action in the preliminary examination.