Engineered nanomaterial-induced lysosomal membrane permeabilization and anti-cathepsin agents

Our plain-English summary of Engineered nanomaterial-induced lysosomal membrane permeabilization and anti-cathepsin agents, by M. Bunderson-Schelvan, A. Holian, R.F. Hamilton (Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 2017).

The study

• Authors: M. Bunderson-Schelvan, A. Holian, R.F. Hamilton
• Journal: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
• Published: 2017;20(4):230-248
• Type of article: Review
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Engineered nanomaterials (ENMs), or small anthropogenic particles approximately < 100 nm in size and of various shapes and compositions, are increasingly incorporated into commercial products and used for industrial and medical purposes. There is an exposure risk to both the population at large and individuals in the workplace with inhalation exposures to ENMs being a primary concern. Further, there is increasing evidence to suggest that certain ENMs may represent a significant health risk, and many of these ENMs exhibit distinct similarities with other particles and fibers that are known to induce adverse health effects, such as asbestos, silica, and particulate matter (PM). Evidence regarding the importance of lysosomal membrane permeabilization (LMP) and release of cathepsins in ENM toxicity has been accumulating. The aim of this review was to describe our current understanding of the mechanisms leading to ENM-associated pathologies, including LMP and the role of cathepsins with a focus on inflammation. In addition, anti-cathepsin agents, some of which have been tested in clinical trials and may prove useful for ameliorating the harmful effects of ENM exposure, are examined.

In plain English

This article is a review, not a new study. The authors described current understanding of how engineered nanomaterials, which are man-made particles roughly under 100 nanometers in size, may lead to disease, with a focus on inflammation. The article is not mainly about asbestos; asbestos appears only as a comparison. The review noted that carbon nanotubes have been described as having asbestos-like properties, and it cited earlier mouse studies in which exposure of the mesothelial lining led to mesothelioma. The main mechanism discussed was damage to the lysosome, a compartment inside cells. That damage releases enzymes called cathepsins and triggers inflammation. The authors stated that several explanations exist for how nanomaterials cause this damage, but none has been proven. They also reviewed drugs that block cathepsins, including cathepsin K and S drugs at various stages of clinical development. The authors noted that there has not yet been enough time for adequate studies of exposed people. The authors concluded that research on blocking the harmful effects of cathepsins released after lysosome damage may lead to prevention or treatment strategies for harmful effects of nanomaterial exposure.

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: Narrative review of published research on engineered nanomaterials, lysosomal membrane permeabilization, cathepsins and anti-cathepsin agents; no new data
• Who was studied: No study population; the review drew on published laboratory, animal and other studies of engineered nanomaterials
• Exposure: Engineered nanomaterials (man-made particles about under 100 nm, of various shapes and compositions, such as carbon nanotubes, metal and metal oxide nanoparticles, quantum dots); asbestos and silica mentioned only as comparisons
• Main results:
  • The review noted that carbon nanotubes have been characterized as having asbestos-like properties, citing earlier studies in which exposure of the mesothelial lining in mice led to mesothelioma
  • The authors described several possible ways nanomaterials may cause lysosomal membrane permeabilization (physical piercing, dissolution in the acidic lysosome, direct interaction with the membrane) and stated that none has been proven
  • The review reported that drugs targeting cathepsins K and S are in various stages of clinical development
  • The review reported that numerous cathepsin S inhibitors are available and some are approved for human therapeutic use
• The authors' conclusion: The authors concluded that future research on inhibiting the harmful effects of cathepsin release after lysosomal membrane damage may provide prevention or treatment strategies for nanomaterial exposure
• Limitations the authors state:
  • The authors stated there has been insufficient time to conduct adequate epidemiology studies of people exposed to nanomaterials
  • The authors stated there is no experimental evidence that high aspect ratio nanomaterials initiate one proposed lipid-based pathway of lysosomal damage
  • The authors stated there are few studies of how long nanomaterials persist in the body over the long term

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Clinical Trial.

Related studies

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• The carcinogenic potential of nanomaterials, their release from products and options for regulating them — H. Becker, F. Herzberg, et al. (2011)
• Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials — H. Nagai, S. Toyokuni (2010)
• Lysosomal enzyme secretion by macrophages during intracellular storage of particles — R.T. Dean, W. Hylton, et al. (1979)
• A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials — V.C. Sanchez, P. Weston, et al. (2011)
• Decoding the molecular enigma behind asbestos and fibrous nanomaterial-induced carcinogenesis — S. Toyokuni, Y. Kong (2025)

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