Acidity-Triggered Transformable Polypeptide Self-Assembly to Initiate Tumor-Specific Biomineralization

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Biomineralization is a natural process crucial for tissue formation.
• Artificially induced biomineralization shows promise for cancer therapy.
• Existing methods face limitations due to insufficient ion-chelating capabilities.

Purpose of the Study:

• To develop a biomineralization-inducing nanoparticle (BINP) for osteosarcoma blockade therapy.
• To enhance the efficacy of antitumor strategies by creating a physical barrier.
• To investigate the therapeutic potential of BINP in preclinical osteosarcoma models.

Main Methods:

• Synthesized BINPs with specific functional moieties for TME responsiveness and ion chelation.
• Administered BINPs intravenously to osteosarcoma-bearing mice.
• Evaluated tumor inhibition, substance exchange blockade, and metastasis suppression.

Main Results:

• BINPs responded to the acidic tumor microenvironment, facilitating cytomembrane insertion.
• A mineralized barrier was formed around tumors, blocking substance exchange.
• Significant tumor inhibition rates of 59.3% (subcutaneous) and 52.1% (orthotopic) were observed.
• Alendronate moiety suppressed osteoclasts, reducing bone dissolution and pulmonary metastases.

Conclusions:

• BINP-initiated selective biomineralization is a promising strategy for osteosarcoma blockade therapy.
• This approach effectively inhibits tumor growth and metastasis.
• BINPs represent a novel alternative for clinical osteosarcoma treatment.