Multiplexed Analysis of the Cellular Uptake of Polymeric Nanocarriers

Polymeric nanocarriers (PNCs) are versatile drug delivery vehicles capable of delivering a variety of therapeutics. Quantitatively monitoring their uptake in biological systems is essential for realizing their potential as next-generation delivery systems; however, existing quantification strategies are limited due to the challenges of detecting polymeric materials in complex biological samples. Here, we describe a metal-coded mass tagging approach that enables the multiplexed quantification of the PNC uptake in cells using mass spectrometry (MS). In this approach, PNCs are conjugated with ligands that bind strongly to lanthanide ions, allowing the PNCs to be sensitively quantitated by inductively coupled plasma-MS. The metal-coded tags have little effect on the properties or toxicity of the PNCs, making them biocompatible. We demonstrate that the conjugation of different metals to the PNCs enables the multiplexed analysis of cellular uptake of multiple distinct PNCs at the same time. This multiplexing capability should improve the design and optimization of PNCs by minimizing biological variability and reducing analysis time, effort, and cost.