Novel thymohydroquinone gallate (THQG) derivative loaded ligand Modified quantum dots as pH-Sensitive Multi-Modal theragnostic agent for cancer treatment

Ummama Saeed; Rubaida Mahmood; Batool Fatima; Dilshad Hussain; Sana Liaqat; Muhammad Imran; Tahir Ali Chohan; Muhammad Saqib Khan; Saeed Akhter; Muhammad Najam-Ul-Haq

doi:10.1016/j.ejpb.2024.114312

Novel thymohydroquinone gallate (THQG) derivative loaded ligand Modified quantum dots as pH-Sensitive Multi-Modal theragnostic agent for cancer treatment

Eur J Pharm Biopharm. 2024 May 10:114312. doi: 10.1016/j.ejpb.2024.114312. Online ahead of print.

Authors

Affiliations

¹ Department of Biochemistry, Bahauddin Zakariya University, Multan, 60800, Pakistan.
² MINAR Cancer Hospital, Pakistan Atomic Energy Commission, Multan, Pakistan.
³ Department of Biochemistry, Bahauddin Zakariya University, Multan, 60800, Pakistan. Electronic address: batoolfatima@bzu.edu.pk.
⁴ HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁵ Biochemistry Section, Institute of Chemical Sciences, University of Peshawar, Pakistan.
⁶ Department of Biochemistry, University of Veterinary and Animal Science, Lahore.
⁷ Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan. Electronic address: najamulhaq@bzu.edu.pk.

PMID: 38735345
DOI: 10.1016/j.ejpb.2024.114312

Abstract

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 (¹³¹I) and Technetium (^99mTc) 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.

Keywords: Antimonene Quantum Dots; Gallic Acid; MCF-7; Targeted drug delivery; Thymoquinone.