Investigation of the anti-cancer impact of nanoparticles loaded with siRNAs against CD47 and IGF-1 in cancer cells

Abstract

The quest for effective cancer treatment is still one of the most demanding challenges in medicine. Cancer immunotherapy is considered the future prospect of cancer treatment, with novel therapeutic strategies targeting tumor microenvironment inhibitory pathways. In the meantime, CD47 and IGF-1, two principal components of the tumor microenvironment, are associated with a significant increase in gene expression, synergistically contributing to tumor growth. Therefore, the present study explores the impact of inhibiting the expression of these two factors on cancer cells. Materials and Methods: The present study was conducted on 4T1 (murine breast cancer) and B16-F10 (murine melanoma) cell lines. Peptide-conjugated Chitosan-based nanoparticles (iron oxide–trimethyl/thiolated chitosan) were used to load and deliver specific CD47- and IGF-1-targeting siRNAs to cancer cells. The impact of nanoparticles on cell survival was investigated using the MTT test, and the expression of genes involved in the growth, proliferation, and invasion of cancer cells was evaluated using the Real-time polymerase chain reaction method. Results: The results of this study showed that suppressed expression of CD47 and IGF-1 in breast cancer and melanoma cancer cells can reduce the survival of the cells, and result in suppressed expression of factors involved in the growth and proliferation, metastasis, and anti-apoptotic pathways of cancer. CD47-specific siRNA-loaded nanoparticles reduce CD47 mRNA expression by about 90%. The most effective apoptosis induction and inhibition of the anti-proliferative, anti-metastasis, and anti-angiogenic pathways, was significantly observed in the combination therapy of the CD47/IGF-1 axis with specific siRNAs of both CD47 and IGF-1 factors.