Aptamer-modified melittin micelles efficiently inhibit osteosarcoma deterioration by inducing immunogenic cell death

Siyu Jia; Yaohui Chen; Can Zhuo; Ming Hu; Chengwei Zhang; Huili Cai; Xinzhi Li; Haidan Chen; Xiang Yu

doi:10.1016/j.colsurfb.2025.114512

Aptamer-modified melittin micelles efficiently inhibit osteosarcoma deterioration by inducing immunogenic cell death

Colloids Surf B Biointerfaces. 2025 Jan 13:249:114512. doi: 10.1016/j.colsurfb.2025.114512. Online ahead of print.

Authors

Siyu Jia¹, Yaohui Chen², Can Zhuo¹, Ming Hu³, Chengwei Zhang², Huili Cai⁴, Xinzhi Li², Haidan Chen⁵, Xiang Yu⁶

Affiliations

¹ The First College of Clinical Medical Science, China Three Gorges University, Yichang, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China; Department of Spinal Surgery, Yichang Central People's Hospital, Yichang, China.
² Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China.
³ State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, China; Key Laboratory of Biomedical Engineering of Hainan Province, One Health Institute, Hainan University.
⁴ The First College of Clinical Medical Science, China Three Gorges University, Yichang, China; Department of Hematology, Yichang Central People's Hospital, Yichang, China.
⁵ The First College of Clinical Medical Science, China Three Gorges University, Yichang, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China; Department of Spinal Surgery, Yichang Central People's Hospital, Yichang, China. Electronic address: [email protected].
⁶ State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, China; Key Laboratory of Biomedical Engineering of Hainan Province, One Health Institute, Hainan University. Electronic address: [email protected].

PMID: 39842274
DOI: 10.1016/j.colsurfb.2025.114512

Abstract

Osteosarcoma (OS) is the most common primary bone malignancy characterized by deposition of an immature osteoid matrix. OS treatment has proven challenging because of the high risk of metastatic progression and recurrence after chemotherapy. Melittin (MLT) is recognized as a potential antitumor candidate to overcome chemotherapy resistance and provoke superior immunostimulatory effects. However, the application of MLT to OS is hampered by severe toxic side effects and a lack of tumor-targeting ability. Herein, a self-assembled nanopolymer named LC09-MLT@F127 was developed by binding MLT with F127 micelles and then modifying an aptamer (LC09) for targeted drug delivery during OS treatment. LC09-MLT@F127 exhibited significant OS-targeting ability in vitro and in vivo owing to the aptamer LC09 decoration. Moreover, LC09-MLT@F127 significantly reduced the hemolytic toxicity of MLT while maintaining its tumor-killing ability. In an orthotopic transplantation model of OS, LC09-MLT@F127 induced immunogenic cell death and facilitated the maturation of dendritic cells (DCs), thereby resulting in the activation of tumor-specific immune responses and the inhibition of OS deterioration. Taken together, these finding suggest that LC09-MLT@F127 may be an encouraging MLT-based immunotherapy option for OS.

Keywords: Aptamer; ICD; Melittin; Osteosarcoma; Targeting.