Development of AS1411 Aptamer-Targeted Solid Lipid Nanoparticles to Improve Anticancer Efficiency of Lawsone

Lawsone (LWS), a naphthoquinone dye known for its anticancer properties, faces challenges with aqueous solubility, which restricts its therapeutic use. Solid lipid nanoparticles (SLNs) are recognized for enhancing the bioavailability of poorly soluble drugs, supporting in targeted drug delivery and reducing toxicity to normal tissues. The purpose of this study was to develop chitosan-coated solid lipid nanoparticles that were loaded with lawsone and conjugated with the AS1411 aptamer (LWS-SLN-Chit-Apt) for evaluating the cytotoxic effects on mouse colon adenocarcinoma cells (C26).

High-shear homogenization and ultrasound methods were used for producing the LWS-SLNs nanoparticles. Several considerations, including dynamic light scattering (DLS), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR), were directed to characterize the properties of the nanoparticles. Next, the nanoparticles were coated with chitosan, then conjugated to AS1411 aptamer, which was confirmed with DLS and gel electrophoresis. Additionally, the encapsulation efficiency of LWS and its release profile were investigated. Cytotoxicity and cellular uptake were evaluated on C26 cells and Chinese hamster ovary (CHO) cells.

The LWS-SLNs and LWS-SLN-Chit-Apt formulations revealed particle sizes of 160±14.8 nm and 350±22.5 nm, with encapsulation efficiencies of 70.72±2.64% and 70.00±4.3%, respectively. Both formulations exhibited a sustained drug release profile over 120 hours. Targeted nanoparticles displayed higher cellular uptake and cytotoxicity in nucleolin-positive cells (C26 cells) compared to nucleolin-negative cells (CHO cells), with no substantial differences observed.

These results illustrated that LWS-SLN-Chit-Apt could be considered as a great candidate for further studies and in vivo trials.