Blood Circulation-Prolonging Peptides for Engineered Nanoparticles Identified via Phage Display

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Prolonging blood circulation time for theranostic nanoparticles is crucial for effective treatment but remains a significant challenge.
• Existing strategies have shown limited success in sustaining nanoparticle residence time in the bloodstream.

Purpose of the Study:

• To explore the potential of M13 bacteriophage-derived peptides in extending the blood circulation time of engineered nanoparticles.
• To identify novel peptides that enhance nanoparticle blood retention and improve theranostic efficacy.

Main Methods:

• In vivo screening of an M13 peptide phage display library to identify blood circulation-prolonging (BCP) peptides.
• Characterization of the identified peptides, including the role of the arginine-glycine-aspartic acid (RGD) motif and platelet binding.
• Fusion of the lead peptide (BCP1) to human heavy-chain ferritin (HFn) for evaluating its pharmacokinetic profile and therapeutic potential.

Main Results:

• Identification of several BCP peptides, with most containing an RGD motif, which was necessary but not sufficient for circulation prolongation.
• Demonstration that RGD-mediated specific binding to platelets is key to the enhanced blood retention of BCP1.
• Fusion of BCP1 to HFn resulted in improved pharmacokinetics, enhanced tumor cell uptake, and optimal anticancer efficacy for encapsulated doxorubicin.

Conclusions:

• Phage display is an effective strategy for discovering novel peptides that significantly prolong blood circulation for engineered theranostic nanoparticles.
• The RGD motif and platelet interaction are critical for the blood retention activity of the identified peptides.
• The BCP1 peptide offers a promising approach to enhance the performance of nanoparticle-based drug delivery systems, particularly in cancer therapy.