Novel thymohydroquinone gallate derivative loaded ligand modified quantum dots as pH-sensitive multi-modal theragnostic agent for cancer treatment.

Background: Nanomedicine, as the combination of radiopharmaceutical and nanocarrier (QDs), is developed for treating cancer. Gallic acid is antimutagenic, anti-inflammatory, and anti-carcinogenic. Typical retention time of gallic acid is approximately 4 to 8 h. To increase the retention time gallic acid is converted to prodrug by adding lipophilic moieties, encapsulating in lipophilic nanoparticles, or liposome formation. Similarly, thymoquinone is powerful antioxidant, anti-apoptotic, and anti-inflammatory effect, with reduced DNA damage.

Methods: In this study, a hydrophilic drug (gallic acid) is chemically linked to the hydrophobic drug (thymohydroquinone) to overcome the limitations of co-delivery of drugs. Thymohydroquinone (THQG) as the combination of gallic acid (GA) and thymoquinone (THQ) is loaded onto the PEI functionalized antimonene quantum dots (AM-QDs) and characterized by FTIR, UV-visible spectroscopy, X-ray powder diffraction, Zeta sizer, SEM and AFM, in-vitro and in-vivo assay, and hemolysis.

Results: The calculated drug loading efficiency is 90 %. Drug release study suggests the drug combination is pH sensitive and it can encounters acidic pH, releasing the drug from the nanocarrier. The drug and drug-loaded nanocarrier possesses low cytotoxicity and cell viability on MCF-7 and Cal-27 cell lines. The proposed drug delivery system is radiolabeled with Iodine-131 (I) and Technetium (Tc) and its deposition in various organs of rats' bodies is examined by SPECT-CT and gamma camera. Hemolytic activity of 2, 4, 6, and 8 μg/mL is 1.78, 4.16, 9.77, and 15.79 %, respectively, reflecting low levels of hemolysis. The system also sustains oxidative stress in cells and environment, decreasing ROS production to shield cells and keep them healthy.

Conclusions: The results of this study suggest that the proposed drug carrier system can be used as a multi-modal theragnostic agent in cancer treatment.