Enhanced core hydrophobicity, functionalization and cell penetration of polybasic nanomatrices

Area of Science:

• Polymer Chemistry
• Nanomedicine
• Materials Science

Background:

• Development of pH-responsive polymer networks is crucial for targeted drug delivery.
• Nanoscale polymer networks offer potential for enhanced cellular uptake and intracellular delivery.
• Controlling nanocarrier properties is key to optimizing therapeutic efficacy.

Purpose of the Study:

• To investigate a novel pH-responsive nanoscale polymer network for nanomedicine applications.
• To assess the control over swelling properties via core hydrophobicity and crosslinking density.
• To evaluate the nanomatrices as carriers for targeted intracellular delivery of macromolecules.

Main Methods:

• Synthesis of poly[2-(diethylamino)ethyl methacrylate-co-t-butyl methacrylate-g-poly(ethylene glycol)] (PDBP) nanomatrices via photo-emulsion polymerization.
• Characterization using NMR, dynamic/electrophoretic light scattering, and electron microscopy.
• In vitro evaluation of cytocompatibility and cellular uptake in NIH/3T3 and A549 cell lines.

Main Results:

• PDBP nanomatrices exhibited tunable swelling ratios (6-22) controlled by crosslinking density.
• Hydrophobicity adjustments allowed control over critical swelling pH without compromising swelling capacity.
• Nanocarriers showed cell-dependent effects on viability and membrane integrity based on crosslinking.
• Enhanced cellular uptake and cytosolic delivery of FITC-albumin were observed, with nuclear localization in a cell-type-dependent manner.

Conclusions:

• PDBP nanomatrices possess tunable swelling properties, making them versatile for drug delivery.
• The developed nanomatrices are cytocompatible.
• These nanocarriers are suitable agents for targeted intracellular delivery of macromolecules.