CD133-targeted delivery of self-assembled PEGylated carboxymethylcellulose-SN38 nanoparticles to colorectal cancer

Poor aqueous solubility of chemotherapeutics such as SN38 (7-ethyl-10-hydroxycamptothecin) and the associated systemic adverse effects are serious limitations of their clinical use. To improve the drug delivery efficiency of such compounds, they were covalently conjugated to hydrophilic macromolecular carriers that specifically deliver the drug moiety to the tumour cells. In the current study, we developed a PEGylated acetylated carboxymethylcellulose conjugate of SN38 which was covalently attached to an aptamer against a cancer stem cell marker, CD133. Then, the designed nanoplatform was used to specifically deliver SN38 to colorectal cancer cells. The results demonstrated that the synthesized conjugate was self-assembled to nanoparticles with 169nm in size and poly dispersity index of 0.11. Besides, the targeted self-assembled nanoparticles could significantly enhance the cellular uptake by CD133-expressing HT29 cell line confirmed by fluorescent microscopy and flow cytometry. Moreover, our results revealed that the targeted self-assembled nanoconjugate exhibited significantly lower IC50 in HT29 cells overexpressing CD133 compared to non-targeted self-assembled nanoconjugate. The promising data suggest that the prepared targeted self-assembled drug conjugate nanoparticles possess the potential to offer the desirable physicochemical properties thereby enhancing the solubility and the therapeutic index of poorly soluble cytotoxic agents.