Modulating Protein-Protein Interactions In Vivo via Peptide-Lanthanide-Derived Nanoparticles for Hazard-Free Cancer...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapeutics

Background:

• Protein-protein interactions (PPIs) are crucial in cellular processes and disease, particularly cancer.
• Peptides show promise for modulating PPIs but suffer from poor stability and cell penetration.
• Existing peptide delivery methods lack efficiency and simplicity for targeted cancer therapy.

Purpose of the Study:

• To develop a simple, one-step method for conjugating peptides with nanoparticles for enhanced cancer therapy.
• To create a novel nanomedicine capable of tumor-specific delivery and potent cancer cell apoptosis induction.
• To establish a generalizable platform for peptide-based nanomedicine development targeting intracellular PPIs.

Main Methods:

• Conjugation of lanthanide-doped nanoparticles with p53-activating peptide (PMI), Bcl2-blocking peptide (BIM), and CD13-binding peptide (iNGR) via mercaptogenic self-assembly.
• In vitro and in vivo evaluation of nanoparticle accumulation, tumor targeting, and cancer cell apoptosis induction.
• Assessment of the biosafety profile of the developed nanomedicine.

Main Results:

• Successful synthesis of lanthanide-doped nanoparticles conjugated with iNGR, PMI, and BIM peptides (LDN-iNGRPMI-BIM).
• Demonstrated tumor-specific accumulation of nanoparticles at target sites.
• Potent induction of cancer cell apoptosis in vitro and in vivo with a favorable biosafety profile.

Conclusions:

• The developed one-step conjugation method offers a therapeutically viable approach for creating peptide-based nanomedicines.
• This strategy can overcome the limitations of peptide therapeutics, potentially reinvigorating peptide drug discovery.
• The targeted nanoparticles show promise for treating various human diseases driven by intracellular PPIs.