Short- and long-term effect of colorectal cancer targeting peptides conjugated to gold nanoparticles in rats' liver and colon after single exposure

Olusola B Adewale; Lynn Cairncross; Hlumisa Xakaza; Nicolas Wickens; Scholastica O Anadozie; Hajierah Davids; Saartjie Roux

doi:10.1007/s43188-021-00108-y

Short- and long-term effect of colorectal cancer targeting peptides conjugated to gold nanoparticles in rats' liver and colon after single exposure

Toxicol Res. 2021 Oct 26;38(3):259-273. doi: 10.1007/s43188-021-00108-y. eCollection 2022 Jul.

Authors

Olusola B Adewale^{1

2}, Lynn Cairncross¹, Hlumisa Xakaza³, Nicolas Wickens⁴, Scholastica O Anadozie^{1

2}, Hajierah Davids³, Saartjie Roux³

Affiliations

¹ Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, 6031 South Africa.
² Present Address: Department of Chemical Sciences, Biochemistry Program, Afe Babalola University, P.M.B 5454, Ado-Ekiti, Nigeria.
³ Department of Human Physiology, Nelson Mandela University, Port Elizabeth, 6031 South Africa.
⁴ Department of Medical Laboratory Science, Nelson Mandela University, Port Elizabeth, 6031 South Africa.

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 µg/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: Colorectal cancer; Diagnosis; Gold nanoparticles; Peptides; Polyethylene glycol.