Arrhythmic Effects Evaluated on Caenorhabditis elegans: The Case of Polypyrrole Nanoparticles

Sumithra Yasaswini Srinivasan1, Pilar Alvarez Illera2, Dmytro Kukhtar3

  • 1Universitat de Autonoma de Barcelona, Institut de Ciència de Materials de Barcelona (ICMAB), 08193, Bellaterra, Barcelona, Spain.

ACS Nano
|August 25, 2023
PubMed

Insights

The nematode Caenorhabditis elegans (C. elegans) serves as a model for testing drug and nanoparticle toxicity. Polypyrrole nanoparticles (Ppy NPs) showed biocompatibility and improved pharyngeal pumping in C. elegans, suggesting potential for cardiac treatments.

Area of Science:

  • Biomedical Engineering
  • Toxicology
  • Nanotechnology

Background:

  • Nanoparticle drug development faces market entry challenges due to cost, development time, and cardiotoxicity.
  • Caenorhabditis elegans (C. elegans) offers a model for systemic toxicity testing, aligning with animal research ethics (3Rs).
  • The C. elegans pharynx shares functional similarities with the human heart, enabling cardiac-related drug and nanoparticle evaluation.

Purpose of the Study:

  • To assess the utility of C. elegans as a model for evaluating drug and nanoparticle effects on cardiac function.
  • To investigate the biocompatibility and pharyngeal effects of polypyrrole nanoparticles (Ppy NPs) in C. elegans.
  • To explore the potential of Ppy NPs in treating cardiac arrhythmia.

Main Methods:

  • Validated C. elegans model by testing FDA-approved drugs (Propranolol, Racepinephrine) for known human cardiac effects.
  • Administered Ppy NPs to C. elegans and assessed survival, growth, reproduction, and transgenerational toxicity.
  • Measured pharyngeal pumping rates in wild-type and mutant C. elegans strains exposed to Ppy NPs.
  • Investigated the role of calcium signaling in Ppy NP-mediated pharyngeal effects.

Main Results:

  • C. elegans accurately reproduced human arrhythmic responses to Propranolol and Racepinephrine.
  • Ppy NPs demonstrated biocompatibility in C. elegans across multiple generations.
  • Ppy NPs significantly increased pharyngeal pumping rates in specific slow-pumping C. elegans mutants.
  • The observed increase in pumping rate was sustained post-excretion and linked to calcium signaling pathways.

Conclusions:

  • C. elegans provides a viable and efficient model for evaluating cardiac effects of drugs and nanoparticles.
  • Ppy NPs are biocompatible and exhibit a positive effect on pharyngeal function in C. elegans.
  • Ppy NPs modulate pharyngeal pumping via calcium signaling, indicating potential therapeutic applications for cardiac conditions.

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