DNA Barcoding-Enabled Tracking of Lipid Nanoparticles: Drug-Loading-Dependent Biodistribution and Tumor...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Lipid nanoparticles (LNPs) are key drug delivery vehicles, but the effect of drug loading (DL) on their behavior is unclear.
• Optimizing DL is vital for LNP efficacy and safety in cancer therapies, reducing nanomaterial exposure.
• Understanding DL impacts is crucial for advancing LNP-based cancer treatments.

Purpose of the Study:

• To investigate how varying drug loading (DL) in lipid nanoparticles (LNPs) affects their in vivo biodistribution and cellular uptake.
• To establish a DNA barcoding method for high-sensitivity tracking of LNPs with different DLs.
• To guide the rational design of LNPs for targeted cancer therapy within the tumor microenvironment (TME).

Main Methods:

• Fabrication of DNA-barcoded LNPs with low (1%), medium (16%), and high (26%) drug loadings using sequential nanoprecipitation.
• Intravenous administration of pooled, barcoded LNPs to tumor-bearing mice.
• Quantification of LNP biodistribution via qPCR and analysis of cellular uptake in the TME.

Main Results:

• High DL LNPs showed preferential spleen accumulation, while low DL LNPs accumulated more in the liver, indicating faster clearance.
• Enhanced uptake of high DL LNPs by tumor-associated macrophages within the TME was observed.
• The DNA barcoding platform enabled sensitive, simultaneous monitoring of LNP behavior, reducing animal use and variability.

Conclusions:

• Drug loading significantly influences LNP biodistribution and tumor-associated macrophage uptake.
• Optimized DL LNPs show potential for targeted delivery within the TME.
• DNA barcoding offers a powerful tool for LNP behavior analysis, aiding in the development of advanced cancer therapies.