Breaking Isolation to Form New Networks: pH-Triggered Changes in Connectivity inside Lipid Nanoparticles

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Growing demand for smart nanomaterials with controlled release capabilities.
• pH gradients in the body offer a stimulus for targeted nanocarrier responses.
• Need for nanomaterials that can alter structure in response to environmental cues.

Purpose of the Study:

• To engineer pH-sensitive lyotropic liquid crystalline nanoparticles.
• To investigate the structural transformation of nanoparticles in response to pH changes.
• To validate the internal structure and symmetry of the engineered nanoparticles.

Main Methods:

• Engineering of lyotropic liquid crystalline nanoparticles.
• Investigation of structural changes at physiological temperatures (pH 7.4 and ≤6).
• Validation using small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM).

Main Results:

• Nanoparticles exhibit reversible structural changes in response to pH.
• At pH 7.4, nanoparticles show an Fd3m structure with discontinuous inverse micellar pockets.
• At pH ≤6, nanoparticles transition to a porous structure with a 2D inverse hexagonal phase (p6mm).
• Direct visualization of the Fd3m internal structure and resolution of inverse micelles using cryo-TEM.

Conclusions:

• Engineered nanoparticles demonstrate sensitive and reversible pH-responsive behavior.
• The structural transition enables potential for controlled release applications.
• Direct visualization confirms structural models and validates nanoparticle design.