Surface chemistry of spiky silica nanoparticles tailors polyethyleneimine binding and intracellular DNA delivery

Cellular delivery of DNA using silica nanoparticles has attracted great attention. Typically, polyethylenei-mine (PEI) is used to form a silica/PEI composite vector. Understanding the interactions at the silica and PEI interface is important for successful DNA delivery and transfection, especially for silica with different surface functionality. Herein, we report that a higher content of hydrogen boning formed between PEI molecules and phosphonate modified silica nanoparticles could slow down the PEI dissolution from the freeze-dried solid composites into aqueous solution than the bare silica counterpart. The pronounced PEI retention ability through phosphonation of silica nanoparticles effectively improves the transfection efficiency due to the high DNA binding affinity extracellularly, effective lysosome escape and high nuclear entry of both PEI and DNA intracellularly. Our study provides a fundamental understanding on designing effective silica-PEI-based nano-vectors for DNA delivery applications.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study demonstrates that a higher content of hydrogen bonding between phosphonate modified silica nanoparticles and PEI molecules can slow down the dissolution of PEI from freeze-dried solid composites into aqueous solution. By utilizing phosphonated silica nanoparticles, the retention ability of PEI is effectively improved, leading to enhanced transfection efficiency through high DNA binding affinity extracellularly, effective lysosome escape, and high nuclear entry intracellularly.