Form Follows Function: Nanoparticle Shape and Its Implications for Nanomedicine

Our plain-English summary of Form Follows Function: Nanoparticle Shape and Its Implications for Nanomedicine, by C. Kinnear, T.L. Moore, L. Rodriguez-Lorenzo, et al (Chemical Reviews, 2017).

The study

• Authors: C. Kinnear, T.L. Moore, L. Rodriguez-Lorenzo, B. Rothen-Rutishauser, A. Petri-Fink
• Journal: Chemical Reviews
• Published: 2017;117(17):11476-11521
• Type of article: Review
• Cited by: 402 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This review is a comprehensive description of the past decade of research into understanding how the geometry and size of nanoparticles affect their interaction with biological systems: from single cells to whole organisms. Recently, there has been a great deal of effort to use both the shape and the size of nanoparticles to target specific cellular uptake mechanisms, biodistribution patterns, and pharmacokinetics. While the successes of spherical lipid-based nanoparticles have heralded marked changes in chemotherapy worldwide, the history of asbestos-induced lung disease casts a long shadow over fibrous materials to date. The impact of particle morphology is known to be intertwined with many physicochemical parameters, namely, size, elasticity, surface chemistry, and biopersistence. In this review, we first highlight some of the morphologies observed in nature as well as shapes available to us through synthetic strategies. Following this we discuss attempts to understand the cellular uptake of nanoparticles through various theoretical models before comparing this with observations from in vitro and in vivo experiments. In addition, we consider the impact of nanoparticle shape at different size regimes on targeting, cytotoxicity, and cellular mechanics.

In plain English

This article was a review, not an original study. The authors summarized roughly the past decade of published research on how the shape and size of engineered nanoparticles affect their interactions with cells and living organisms. They covered theoretical and computer models, laboratory cell experiments and animal experiments. Asbestos appeared only as a point of comparison: the authors noted that high aspect ratio nanomaterials have been studied for toxicity because they resemble long-fiber asbestos. Among the studies reviewed, one reported that long carbon nanotubes placed in the abdominal cavity of mice produced granulomatous inflammation comparable to long-fiber amosite. Another found that cellulose nanocrystals caused a lower cytotoxic response than multiwalled carbon nanotubes and crocidolite asbestos fibers. In a third, PEG-coated nanotubes injected into the bloodstream of nude mice showed no significant signs of toxicity. The authors concluded that exposure to airborne high aspect ratio particles can potentially lead to serious long-term consequences such as mesothelioma. They also stated that few comparable, fully characterized studies exist.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published research (theoretical models, in vitro and in vivo studies) on nanoparticle shape
• Who was studied: Published studies from about the past decade, grouped into simulations and theoretical models, in vitro cell experiments, and in vivo (mostly animal) experiments
• Exposure: Engineered nanoparticles of different shapes (spheres, rods, discs, cubes, filaments, fibers, 2D sheets such as graphene), both inorganic (metals, semiconductors, oxides) and organic (polymers, carbon materials). Asbestos discussed only as a comparison for high aspect ratio materials.
• Main results:
  • In a reviewed mouse study, carbon nanotubes of varying lengths were instilled into the peritoneal cavity of female C57Bl/6 mice. Long nanotubes produced granulomatous inflammation on the diaphragm comparable to long-fiber amosite.
  • A reviewed in vitro study comparing cellulose nanocrystals (CNC), multiwalled carbon nanotubes and crocidolite asbestos fibers found that CNC elicited a lower cytotoxic response than the nanotubes and asbestos.
  • In a reviewed study, PEG-coated carbon nanotubes given by intravenous injection showed no significant signs of toxicity in nude mice. The authors took this as pointing to the importance of route of administration.
  • Across the in vitro studies reviewed, rod-shaped particles generally appeared to be taken up by cells more favorably than spherical particles. Very high aspect ratio particles could evade phagocytosis because of their length.
  • After systemic introduction, spheres and short rods tended to accumulate more in the liver. Higher aspect ratio particles concentrated more in the spleen and lungs.
• The authors' conclusion: The authors concluded that high aspect ratio nanomaterials display biological effects similar to those of high aspect ratio asbestos. In their view, exposure to nanopowders or aerosolized high aspect ratio particles can potentially lead to serious long-term consequences such as mesothelioma, while fewer adverse effects were found with systemic administration than through the lung. They called for comprehensive, well-designed studies.
• Limitations the authors state:
  • The variables involved (material, mechanical properties, cell type, surface ligands) are so varied that there are few comparable studies from which robust conclusions can be drawn.
  • Comprehensive and fully characterized studies are sparse in the literature.
  • Most cytotoxicity and cell-mechanics studies used flat 2D cell cultures rather than more realistic 3D models.
  • Nanoparticle concentrations used in in vitro exposures are often higher than would be predicted in vivo.

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, biopersistence.

Related studies

• Nanomedicine: experts state safety concerns regarding carbon nanotubes have been allayed by chemistry — P. Nagda (2013)
• Nanoparticles and potential human health implications: past and future directions. Preface — M. Gulumian, V. Vallyathan (2010)
• An in vitro testing strategy towards mimicking the inhalation of high aspect ratio nanoparticles — C. Endes, O. Schmid, et al. (2014)
• Curcumin loaded PLGA-poloxamer blend nanoparticles induce cell cycle arrest in mesothelioma cells — L. Mayol, C. Serri, et al. (2015)
• Paclitaxel-loaded expansile nanoparticles enhance chemotherapeutic drug delivery in mesothelioma 3-dimensional multicellular spheroids — H. Lei, S.C. Hofferberth, et al. (2015)
• In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility — T.J. Brunner, P. Wick, et al. (2006)

Browse return to medical research.