Artemisinin-loaded polylactic acid nanoparticles alleviate 1.2 N,N-dimethylhydrazine-induced colorectal cancer in Albino rats

Abstract Background Colorectal cancer (CRC) is one of the most fatal malignant neoplasms around the world. Artemisinin (ART) displays broad anticancer properties with some drawbacks. Therefore, we tried to enhance the anticancer efficacy of ART by loading it into polylactic acid nanoparticles (ART-PLA NPs) and investigated its ameliorative effect against 1.2 N , N -dimethylhydrazine (DMH) induced CRC through targeting wnt/β-catenin and NF-κB pathways. Methods Sixty male rats were allocated into six groups: control, ART, ART-PLA NPs, DMH, DMH + ART and DMH + ART-PLA NPs. Rats were administered 7 mg/kg /bw of ART and ART-PLA NPs daily for 24 weeks and 40 mg/kg bw, i.p of DMH once a week for successive 12 weeks. Results ART and ART-PLA NPs significantly decreased carcinoembryonic antigen (CEA) serum concentration, inhibit NF-κB pathways through mitigation of the proinflammatory cytokines TNF-α, IL-1β, and NF-kB-p65, and enhanced the anti-inflammatory cytokine IL-10 colonic levels. The histopathological study of DMH group revealed moderate to severe dysplasia, different types of adenoma and adenocarcinoma with reduced colonic mucous secretion and increased fibrous tissue deposition. ART-PLA NPs treatment was more powerful than ART as indicated by fewer and smaller colorectal tumors, higher mucous secretion and mild fibrous tissue deposition. DMH treatment upregulated β-catenin gene expression in the colonic mucosa. Surprisingly, β-catenin mRNA level appeared significantly lower in DMH + ART and DMH + ART-PLA NPs groups than DMH group, with a more pronounced decline in the ART-PLA NPs group. While, adenomatous polyposis coli ( APC ) gene expression was significantly downregulated in DMH group than other groups, and its expression appeared potentiated by DMH + ART and DMH + ART-PLA NPs treatments. Moreover, the gene expression findings were confirmed by western blot analysis of β-catenin and APC protein expression that recorded the same expression pattern. Conclusion This study suggests ART-PLA NPs attenuated cancer cell proliferation via targeting wnt/β-catenin and NF-κB pathways than free ART. Thus it should be considered when formulating prophylactic and therapeutic strategies for CRC.