Shear Stress-Responsive Peptide Cubic Vesicles Assembled from Membranes with Different Curvatures

Area of Science:

• Biomaterials Science
• Nanotechnology
• Vascular Biology

Background:

• Stenotic blood vessels exhibit significantly increased blood flow shear stress compared to normal vessels.
• Current drug delivery systems (DDSs) lack responsiveness to these critical biophysical changes.
• Developing shear stress-responsive carriers is crucial for targeted therapy in vascular diseases.

Purpose of the Study:

• To engineer novel peptide cubic vesicles (PCVs) that respond to varying shear stress levels.
• To investigate the structural integrity and drug release characteristics of PCVs under physiological and pathological shear stress.
• To explore the potential of mechanical stimulation-responsive DDSs for treating vascular occlusion-inducing diseases.

Main Methods:

• Synthesized two types of sheet-forming amphiphilic polypeptides: planar (S10L12S10) and curved (S26L14).
• Constructed PCVs by mixing S10L12S10 and S26L14 in specific molar ratios (2:1 and 1:1).
• Evaluated PCV deformation and drug release under varying shear stress conditions (1 Pa and 10 Pa).

Main Results:

• Successfully constructed PCVs with distinct roles for planar and curved polypeptide sheets.
• PCVs deformed under pathological shear stress (10 Pa) but remained stable at physiological levels (1 Pa).
• PCVs released 84% of encapsulated cargo in response to simulated pathological flow.

Conclusions:

• PCVs demonstrate shear stress-responsive behavior, deforming under pathological conditions.
• This mechanical responsiveness enables targeted drug release in diseased vasculature.
• Mechanical stimulation offers a promising paradigm shift for vascular disease treatment, potentially reducing drug dosage and side effects.