Abstract: Glutamine is widely recognized as a core metabolic substrate for highly proliferating cells and is critically involved in the development and progression of malignant tumors. Targeting this metabolic vulnerability, a novel boron-based carrier, peptide-RGD-glutamine (Q)-boron (P-RQB), was designed and synthesized for application in boron neutron capture therapy (BNCT). This agent was constructed as a multifunctional molecule integrating three distinct modules: a carborane core serving as a high-boron-density unit, a cyclic RGDfK peptide moiety enabling specific targeting of α_Ⅴβ₃ integrin overexpressed in tumor vasculature, and a glutamine-mimicking side chain designed for active cellular uptake via the SLC1A5 transporter through a dual-pathway mechanism. The rational design aimed to exploit both receptor-mediated and nutrient transporter-mediated pathways for enhanced tumor selectivity and boron delivery efficiency. To evaluate the binding behavior and stability of P-RQB, molecular dynamics simulations were conducted. The simulation results reveal that P-RQB forms stable complexes with both α_Ⅴβ₃ integrin and the SLC1A5 transporter, as evidenced by minimal fluctuations in the root mean square deviation (RMSD) over time. The strong affinity and stable binding support the hypothesized dual-targeting mechanism. Subsequently in vitro experiments were carried using 4T1 breast cancer cells. The results show that the boron uptake mediated by P-RQB is 7.39×10¹¹ boron atoms per 10⁶ cells. This uptake is significantly suppressed in the presence of excess α_Ⅴβ₃ integrin, confirming the competitive and receptor-specific nature of the internalization process. Additional inhibition assays using SLC1A5 blockers further validates the transporter-mediated uptake route. In vivo studies were carried out in tumor-bearing mouse models. Following a single intravenous injection, the boron concentration in tumor tissue was monitored over time. A peak value of 21.32 ppm is observed at 24 h post-injection, with a high tumor-to-normal tissue (T/N) ratio of 5.23, indicating selective accumulation. The boron retention in tumors remains high over 48 h, while rapid clearance is seen in normal tissues. Upon neutron irradiation, the survival rate of tumor clones is effectively reduced to 4.62%, demonstrating significant therapeutic efficacy. Histopathological analysis further reveals extensive damage in tumor regions but minimal injury in surrounding normal tissues. By combining glutamine mimicry with a carborane backbone and a tumor-targeting peptide, P-RQB achieves dual-level targeting—both tissue-selective localization and enhanced cellular internalization. This approach markedly increases intra-tumoral boron concentration and improves radiotherapeutic precision. The study not only validates P-RQB as a promising BNCT agent but also introduces a general design strategy for boron carrier development, offering new insights into targeting metabolic pathways for cancer theranostics. This methodology may be extended to other nutrient transporters or tumor-specific receptors, broadening its application in targeted radionuclide therapy.