Determination of the interior pH of lipid nanoparticles using a pH-sensitive fluorescent dye-based DNA probe

Lipid nanoparticles (LNPs) with pH-sensitive DNA probes can effectively monitor the internal pH at a single particle level.

• The pH of LNP-encapsulated probes closely follows changes in the external environment's pH.
• This behavior suggests that clinically approved LNP RNA systems are highly permeable to protons.
• DNA probes were successfully encapsulated within LNPs, evidenced by an inter-probe signal indicating high concentration.
• The pH-sensitive DNA probe can be incorporated into LNPs to enable monitoring at the level of individual particles.
• Direct visualization of the internal pH of LNPs was achieved using confocal microscopy under varying ionic strength conditions.

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