## 3 Results
### Free Radical Scavenging and Cellular Uptake Assay  
As the active group of LA-1, loganin was reported to be able to reduce oxidative stress [19]. Therefore, we assessed the free radical scavenging activity of LA-1 using electron spin resonance (ESR). LA-1 significantly reduced the ESR signal intensity of NO, -OH, and DPPH radicals (Figure S5), indicating the conjugation with RGDV may not affect the  
Figure 2: Characterization of LA\(-\)1 and loganin. (**A**) The FT\(-\)IR spectra of LA-1 and loganin. (**B**) The UV spectra of LA\(-\)1 and loganin. (**C**) Particle size distribution and zeta potential of LA\(-\)1 and loganin. (**D**) TEM images of LA\(-\)1 and loganin. (**E**) SEM images of LA\(-\)1 and loganin. (**F**) AFM images of e LA\(-\)1 and loganin.  
antioxidant capacity of loganin. To validate the integrin targeting ability of LA-1, an avp83 highly expressing cell line, BEnd.3, was used for uptake assay. Initially, the cytotoxicity of LA-1 and loganin on BEnd.3 cells was determined using the MTT assay. After 24 h treatment with LA-1 or loganin, no significant change in cell viability was observed from all three concentrations. MTT assay results indicated that LA-1 did not exhibit significant cytotoxicity under the given conditions (Figure S6). Then, the middle concentration in MTT assay (6.25 uM) was chosen for cellular uptake assay. BEnd.3 cells were incubated with 6.25 uM of LA-1 or loganin for 3 or 6 h, respectively. Intracellular LA-1 and loganin were then extracted and quantified by LC-MS/MS. The intracellular amount of loganin reached a plateau after 3 h of incubation, while LA-1 continued to accumulate, indicating that the modified LA-1 has enhanced cellular uptake efficiency compared to loganin. After 3 h of incubation, the cellular uptake of LA-1 was approximately 670-fold higher than that of loganin, and after 6 h of incubation, the uptake increased to approximately 2148-fold higher. This demonstrates that conjugation with RGDV significantly enhanced cellular uptake efficiency (Figure 3A). To validate the increase in cellular uptake of LA-1 is mediated by integrin \(\alpha\)v\(\beta\)3, we pretreated BEnd.3 cells with 100 uM of integrin \(\alpha\)v\(\beta\)3 inhibitor c(RGDfK) for 1 h, then performed cellular uptake assay as described above. As expected, the cellular uptake of LA-1 decreased significantly (by approximately 3-fold) with the presence of c(RGDfK) (Figure 3B).  
Figure 3: Evaluation of the neuroprotective and antioxidant effects of LA-1 and loganin. (**A**) Comparative Uptake of LA-1 and Loganin in BEnd.3 cells. (**B**) Drug of LA-1 uptake over time was measured by HPLC-MS after pre-addition of the avp83 inhibitor c(RGDfk). (**C**) Representative images of BEnd.3  
cells stained with DCFH-DA (green) and Hoechst (purple) under different treatment groups. (**D**) Quantification of the percentage of DCFH-DA relative fluorescence intensity in each treatment group. (**E**) Flow cytometry analysis of DCFH-DA stained BEnd.3 cells to detect ROS levels under different treatment conditions. (**F**) Quantification of the percentage of DCFH-DA relative fluorescence intensity in each phase. (**G**) LA-1 and loganin's protective effects against TBHP-induced cytotoxicity. Data were presented as mean \(\pm\) SD, with statistical significance indicated as \({}^{*}p<0.05\), \({}^{**}p<0.01\), and \({}^{***}p<0.001\). \({}^{***}p<0.0001\), ns represents not significant, n = 3.