Letter to the Editor Concerning "Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles"

TL;DR

This paper discusses the challenges of accurately measuring the size and loading of drug-delivery nanoparticles, highlighting errors in current methods and proposing measurement error models to improve reliability.

Contribution

It critically examines existing nanoparticle sizing techniques, identifies sources of error, and suggests measurement error models to enhance accuracy in nanoparticle characterization.

Findings

Large errors in size distribution measurements contradict validation claims.

Measurement errors can bias fluorescence intensity and size correlation analyses.

Measurement error models have potential to improve nanoparticle sizing accuracy.

Abstract

The vexing error of excess variance in the sizing of single particles degrades accuracy in applications ranging from quality control of nanoparticle products to hazard assessment of nanoplastic byproducts. The particular importance of lipid nanoparticles for vaccine and medicine delivery motivates this comment on a publication$^{\textrm{1}}$ in ACS Nano. In ref 1, the benchmark measurements of a nanoparticle standard manifest large errors of the size distribution that contradict the claim of validation. Such errors can bias the correlation of fluorescence intensity as an optical proxy for the molecular loading of lipid nanoparticles and give misleading insights from power-law models of intensity$-$size data. Looking forward, measurement error models have the potential to address this widespread issue.