Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Short- and long-term effect of colorectal cancer targeting peptides conjugated to gold nanoparticles in rats' liver and colon after single exposure

  • Adewale, Olusola B. (Department of Biochemistry and Microbiology, Nelson Mandela University) ;
  • Cairncross, Lynn (Department of Biochemistry and Microbiology, Nelson Mandela University) ;
  • Xakaza, Hlumisa (Department of Human Physiology, Nelson Mandela University) ;
  • Wickens, Nicolas (Department of Medical Laboratory Science, Nelson Mandela University) ;
  • Anadozie, Scholastica O. (Department of Biochemistry and Microbiology, Nelson Mandela University) ;
  • Davids, Hajierah (Department of Human Physiology, Nelson Mandela University) ;
  • Roux, Saartjie (Department of Human Physiology, Nelson Mandela University)
  • Received : 2021.05.23
  • Accepted : 2021.09.22
  • Published : 2022.07.15
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Abstract

Peptides play important roles in the diagnosis, prognostic predictors, and treatment of various kinds of cancer. Peptides (p.C, p.L and p.14), derived from the phage display peptide libraries, specifically binds to colorectal cancer (CRC) cells in vitro. To allow tumor specificity and selectivity for in vivo diagnosis of CRC, biotinylated p.C, p.L and p.14 were conjugated to AuNPs (14 nm) via the biotin-streptavidin interaction. Male Wistar rats were intravenously injected with a single dose (100 ㎍/kg body weight) of AuNPs (citrate-AuNPs, PEG-AuNPs, p.C-PEG-, p.L-PEG- and p.14-PEG-AuNPs). Animals were monitored for behavioral changes, and sacrificed either 14 days or 84 days post-injection. Biochemical changes, oxidative stress, and histology of the liver and colon were assessed. No significant changes were noted in the rats injected with all the AuNPs, except p.L-PEG-AuNPs that caused significant toxicity (p<0.05) 14 days post-exposure when compared to control group, as evidenced by increased relative liver weight, increased malondialdehyde levels and histological changes in the liver. These changes, however, returned to normalcy 84 days post-injection. It can be concluded, based on these findings, that p.L induced a transient toxicity in rats after a single intravenous injection, and can therefore be considered non-toxic long-term after a single exposure.

Keywords

Acknowledgement

This work was supported by the National Research Foundation, South Africa [Grant Number 101132] to Olusola B. Adewale. The authors also acknowledge the technical assistance by Mr. Lawyer Mabulu and Ms. Jabu Madubedube of the Department of Biochemistry and Microbiology, Nelson Mandela University, South Africa, and Prof. M. Meyer of University of the Western Cape, South Africa, for donating the peptides used.

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