Chemistry. 2022 Sep 18. doi: 10.1002/chem.202200947. Online ahead of print.
ABSTRACT
Transmission electron microscopy (TEM) observations of negatively stained cell membrane (CM)-coated polymeric nanoparticles (NPs) reveal a characteristic core-shell structure. However, negative staining agents can create artifacts that complicate the determination of the actual NP structure. Herein, we demonstrate with various bare polymeric core NPs, such as poly(lactic-co-glycolic acid) (PLGA), poly(ethylene glycol) methyl ether-block-PLGA, and poly(caprolactone), that certain observed core-shell structures are actually artifacts caused by the staining process. To address this issue, we use fluorescence quenching to quantify the proportion of fully coated NPs and use statistical TEM analysis to identify and differentiate whether the observed core-shell structures of CM-coated PLGA (CM-PLGA) NPs are due to artifacts or to the CM coating. Integrated shells in TEM images of negatively stained CM-PLGA NPs are identified as artifacts. The present results challenge current understanding of the structure of CM-coated polymeric NPs and encourage researchers should use the proposed characterization approach to avoid misinterpretations.
PMID:36116117 | DOI:10.1002/chem.202200947
