The development of mitochondria-targeted quercetin for rescuing Sertoli cells from oxidative stress

Background and purpose: The imbalance between reactive oxygen species (ROS) production and endogenous antioxidant capacity leads to oxidative stress, which may damage several cellular functions, particularly spermatogenesis. This condition is a leading cause of male infertility, so controlling ROS levels is crucial. The ROS level can be controlled by supporting the endogenous antioxidant system through antioxidant therapy. Mitochondria are the prime target for antioxidant therapy due to the majority of endogenous ROS produced in mitochondria and their critical role in providing energy during fertilization. This research aimed to develop mitochondria-targeted hybrid nanoplatforms by combining liposomes with dequalinium’s mitochondriotropic agent (DQ) to deliver quercetin for targeted antioxidant therapy to mitochondria. Experimental approach: The quercetin-loaded nanocarrier was constructed using the hydration method. We varied the concentration of DQ to investigate its impact on physical characteristics, encapsulation efficiency, intracellular trafficking, and in vitro antioxidant activity. Findings/Results: The impact of different DQ densities on particle size, encapsulation efficiency, and mitochondria targeting was insignificant. However, lowering the DQ density reduced the zeta potential. Minimizing oxidative stress on TM4 cells was only achieved with low-density DQ (Q-LipoDQ LD), while high-density DQ (Q-LipoDQ HD) failed to mitigate the negative impact. Conclusion and implications: According to the findings, LipoDQ LD preserves a promising potential as mitochondria-targeted nanoplatforms and validates the importance of mitochondria as a target for antioxidant therapy.