Nanostructured lipid carriers loaded with capecitabine modulate apoptosis via IL-6 signaling: A novel approach to targeted cancer therapy

Purpose: To examine the impact of capecitabine-loaded nanostructured lipid carriers (NLC) on cancer cell death mechanisms and apoptosis through interleukin-6 (IL-6) signaling system. Method: In a triplicate MTT assay, cell viability was assessed using 100 μg/mL capecitabine-loaded nanostructured lipid carrier (NLC) formulation. Apoptotic DNA degradation was determined by DNA fragmentation analysis. The molecular processes behind cellular responses were clarified by gene expression profiling of IL-6 pathway components. The formulations were characterized using zeta potential, particle size, and polydispersity index (PDI). Furthermore, morphological analysis, MTT testing, DNA fragmentation assay, and qRT-PCR were used to examine gene expression of interleukin cytokines IL-6, IL-6R, gp130, Bcl-2, Bax, NF-kB, and JAK-STAT. Results: Microscopic examination of cell lines revealed morphological alterations suggestive of cell death and apoptosis. Results from MTT assay showed that nano-formulation had a much lower IC50 (8 μg/mL) compared to pure drug (48 μg/mL). There were statistically significant (p < 0.05) differences between nano formulation and pure drug in each treatment concentration. Expression of inflammatory and apoptotic genes was significantly lower in pure and Nano-Cap treated cell lines compared to control (p < 0.05). However, treatment with Nano-Cap significantly reduced expression of inflammatory and apoptotic markers compared to pure drug (p < 0.05). Furthermore, level of Bax was significantly increased (p < 0.001) in Nano-Cap-treated cell lines compared to pure drug and control Conclusion: Capecitabine-loaded nanostructured lipid carriers (NLC) are more effective than pure drug in treating colon cancer. The results may contribute to developing more effective, targeted cancer therapies and personalized treatment strategies by elucidating the interplay between nanoparticle drug delivery, chemotherapy agents, and intracellular signaling pathways.