Methodologies and approaches for the analysis of cell–nanoparticle interactions

Abstract

How to study nanoparticle-cell interactions is the key question that puzzles researchers in the fields of nanomedicine as well as in nanotoxicology. In nanotoxicology, the amount of nanoparticles internalized by the cells or bound to the external surfaces of cells determines the toxic profile of those particles. In medical applications, cellular uptake and binding of medically effective nanoparticles decides their efficacy. Despite the importance of understanding the extent and mode of nanoparticle-cell interactions, these processes are underinvestigated, mainly due to the lack of suitable user-friendly methodologies. Here we discuss the advantages and limitations of currently available (and most advanced) microscopic, spectroscopic, and other bioanalytical methods that could be used to assess cell-nanoparticle interactions either qualitatively or quantitatively. Special emphasis is given to the methods that enable analysis and identification of nanoparticles at single-cell level, and allow intracellular localization and speciation analysis of nanoparticles. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Intracellular Transport of Silver and Gold Nanoparticles and Biological Responses: An Update

“…Several methods, reviewed in Ivask et al [ 107 ], can be employed to study the cellular uptake, distribution and speciation of metal NPs in cells. Here, we highlight only the most useful techniques for a direct observation of metal NPs, and for the quantitative evaluation of biodistribution, focusing on our experience in the detection of AgNPs and AuNPs.…”

Engineering of Nebulized Metal–Phenolic Capsules for Controlled Pulmonary Deposition

“…In this technique, cell suspensions are prepared from target organs, incubated with antibodies that have been labeled with heavy metal isotopes as cell markers, and analyzed by ICP-MS on a single-cell basis for antibody and capsule-associated signal. [37] Tm-labeled (Fe III -TA) 1 , (Fe III -TA) 3 , and (Fe III -TA) 6 capsule suspensions (1 × 10 7 capsules in 100 µL DPBS) were directly nebulized into the lungs of experimental mice, whereas control mice received DPBS only. The animals were euthanized 20 h later, and suspensions of single cells and capsules from enzymatically digested whole lungs were analyzed by MC.…”

Quantification of silver nanoparticles taken up by single cells using inductively coupled plasma mass spectrometry in the single cell measurement mode

“…The impact of nanoparticles, NPs, on cells is a key question in biomedical applications as well as in nanotoxicology and numerous analytical methods such as uorescence and electron microscopy, mass spectrometry imaging, and mass and ow cytometric approaches have been applied to understand the extent and mode of cell-NP interactions. [1][2][3][4] However, such methodologies are still in their infancy to resolve cell-associated NP uptake and the analysis of NPs at the single cell level remains a challenge. Most traditional methods involve the bulk analysis of a large number of cells by lysis, extraction or digestion, only providing average data from thousands of cells and masking the stochastic diversity of individual cellular responses.…”