Yuzhu Zhou,1,2,* Liwen Chen,1,2,* Chao Shang,1,* Yang Hong,2 Hui Zhang3 

1Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, Liaoning, 110022, People’s Republic of China; 2Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Department of Urology, Shengjing Hospital, China Medical University, Shenyang, Liaoning, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yang Hong, Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, People’s Republic of China, Email hongy@sj-hospital.org Hui Zhang, Department of Urology, Shengjing Hospital, China Medical University, Shenyang, Liaoning, People’s Republic of China, Tel/Fax +86-24-31927903, Email zhangh10@sj-hospital.org

Introduction: Glioma is the most common primary malignant tumor in the brain, characterized by rapid growth, strong invasiveness, and unclear lesion boundaries. Current drug treatments have the problems of weak targeting and poor therapeutic effect. TMVP1 is a tumor-targeting peptide that specifically binds to FLT4, a receptor involved in glioma angiogenesis. Its high affinity and selectivity for FLT4 make it an ideal candidate for targeted drug delivery. By functionalizing TMZ-loaded liposomes with TMVP1 (TMZ@Lip-TMVP1), we aimed to enhance glioma-specific targeting and therapeutic efficacy.
Methods: FLT4 was validated as a therapeutic target for glioma by bioinformatics analysis, RT-qPCR, and immunofluorescence experiments. The targeting ability of TMVP1 to FLT4 was confirmed using colocalization and surface plasmon resonance (SPR) experiments. The physicochemical properties of TMZ@Lip-TMVP1, including potential, particle size, TMZ encapsulation efficiency, and peptide coupling rate, were characterized. In vitro cytotoxicity tests were performed to evaluate biocompatibility and therapeutic efficacy. In addition, the targeted delivery and therapeutic impact of TMZ@Lip-TMVP1 were evaluated in subcutaneous tumor-bearing nude mice.
Results: Based on bioinformatics, RT-qPCR, and immunofluorescence results, FLT4 was identified as a reliable therapeutic target for glioma. Colocalization and SPR experiments showed that TMVP1 could effectively bind to FLT4. TMZ@Lip-TMVP1 had good stability and physicochemical properties. Cytotoxicity experiments showed that liposome microcapsules had good biocompatibility, and TMZ@Lip-TMVP1 significantly enhanced the killing effect on glioma cells compared with unmodified liposomes. In vivo experiments showed that TMZ@Lip-TMVP1 could effectively target FLT4 and improve the therapeutic effect of glioma mouse models.
Discussion: The results confirmed that TMZ@Lip-TMVP1 can efficiently deliver TMZ to glioma cells by targeting FLT4, improving the therapeutic effect. This targeted delivery platform provides a promising approach for glioma treatment. In addition, the modular nature of this molecular probe system allows functional adjustment by modifying the coating material, which may enable wider applications in targeted drug delivery and precision medicine.

Keywords: glioma, FLT4, TMVP1 peptide, temozolomide, tumor homing peptide