Specific targeting delivery to MUC1 overexpressing tumors by albumin-chitosan nanoparticles conjugated to DNA aptamer

Background and objective : MUC1 is overexpressed on the surface of tumor cells such as breast, ovary,prostate, cervix, colon, pancreas, and lung, whereas it is expressed to a limited extent in normal cells, it is an appropriate target for chemotherapeutics[1]. Aptamers (Apt) are single-stranded RNA or DNA oligonucleotides that fold into well-defined 3-dimension structures, which are able to recognize molecules, such as phospholipids, proteins, nucleic acids, and sugars, [2].Apt show high affinity and specificity to the cell-specific receptors [3].Chitosan-coated human serum albumin nanoparticles were functionalized by MUC1 aptamer to obtain a selective drug carrier toward cancers overexpressing MUC1.Material and method: HAS-CS- APT NPs was synthesized and cellular uptake, specific targeting capacity and cytotoxicity against cells overexpressing MUC1 receptors was determined. particle size and drug loading capacity and physicochemical properties was determined. Also conjugation of Apt was shown with confocal microscopy.Findings: The IC50 of targeted nanoparticles was 28 and 26% of free paclitaxel in MCF7 and T47D cells at 48 h, respectively. Confocal laser scanning electron microscopy showed that aptamer conjugation and positive charge increase the cellular uptake. 66% of paclitaxel was released within 32 h, but 100% of drug was released at pH = 5.5 (similar cancer cells). The paclitaxel plasma amount was at a good level of 17.6% at 2 h for increasing the chance of cellular uptake. Particle size was less than 200 nm. The negative charges of albumin nanoparticles were shifted to positive charges by surface modification with chitosan, and MUC1 was conjugated through an acrylate spacer. The cytotoxicity of targeted nanoparticles was significantly more than non-aptamer nanoparticles, and also the chitosan-coated nanoparticles had more cytotoxic effects than the negatively charged albumin nanoparticles.Conclusion: The present research proposed a novel strategy based on nanoparticle surface modification for the specific delivery of hydrophobic anticancers to overexpressing MUC1 tumors. The HSA-CS-Apt NPs showed enhanced cellular uptake, increased specific targeting capacity, and increased cytotoxicity against cells overexpressing MUC1 receptors. The enhanced anti-tumor effect of HSA-CS-Apt NPs was attributed to the small particle size, enhanced solubility and permeation to cells, the positive charge of CS, and active targeting by Apt.

Keywords:

Drug delivery-MUC1-HSA-CS-Aptnanoparticels- tumor