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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunotherapy

Background:

• Osteosarcoma (OS) is a primary bone cancer with high metastatic potential and resistance to chemotherapy.
• Melittin (MLT) shows anti-tumor promise but suffers from toxicity and poor targeting in OS treatment.
• Developing targeted drug delivery systems is crucial for effective OS therapy.

Purpose of the Study:

• To develop a targeted nanopolymer, LC09-MLT@F127, for enhanced osteosarcoma treatment.
• To evaluate the in vitro and in vivo efficacy and safety of LC09-MLT@F127.
• To investigate the immunotherapeutic potential of LC09-MLT@F127 in osteosarcoma.

Main Methods:

• Self-assembly of a nanopolymer by conjugating melittin (MLT) with F127 micelles.
• Modification of the nanopolymer with an aptamer (LC09) for osteosarcoma targeting.
• In vitro and in vivo evaluation of targeting ability, toxicity, anti-tumor efficacy, and immunogenic cell death in an OS model.

Main Results:

• LC09-MLT@F127 demonstrated significant targeting of osteosarcoma cells in vitro and in vivo.
• The nanopolymer reduced melittin's hemolytic toxicity while preserving its tumor-killing capacity.
• LC09-MLT@F127 induced immunogenic cell death, promoted dendritic cell maturation, and activated anti-tumor immune responses, inhibiting OS progression.

Conclusions:

• LC09-MLT@F127 is a promising targeted nanopolymer for osteosarcoma treatment.
• This novel formulation offers reduced toxicity and enhanced immunotherapeutic effects compared to native melittin.
• LC09-MLT@F127 represents a potential new immunotherapy strategy for osteosarcoma.