MUC1 aptamer conjugated to chitosan nanoparticles, an efficient targeted carrier designed for anticancer SN38 delivery.

Molecularly targeted therapy is of great interest for diagnosis and treatment of cancerous cells due to its low toxicity for normal cells. In this study, chitosan was utilized as a promising carrier for delivery, and aptamer (Apt) was employed for active targeting of SN38 to colon cancer. SN38 cannot be used clinically due to its poor solubility and high toxicity. Developing nanoparticles (NPs) of drug-polymer conjugates can be a good candidate for overcoming such problems. N-Carboxyethyl chitosan ester (CS-EA) was synthesized as an intermediate for conjugation of SN38 to chitosan. MUC1 DNA aptamer with 5'-NH2 functional group was conjugated to the self-assembled conjugate as a targeting agent. Prepared NPs had smooth and spherical morphology with 200 nm particle size. Conjugation of aptamer was confirmed by gel electrophoresis. In vitro cytotoxicity of NPs was assessed by HT-29 as MUC1 positive cell line through MTT assay. Aptamer conjugated NPs (Apt NPs) were more toxic than non-targeted NPs, however they were as toxic as free drug. Cellular uptake and targeting ability of prepared NPs were also confirmed via confocal microscopy. As a conclusion, prepared CS-SN38-Apt NPs can increase efficacy of drug SN38 through increasing solubility and specific delivery to the target tissue.