Nanoparticles for combined photo- and chemo-dynamic therapy of cancer cells involving endogenous glutathione depletion.

Background: Reactive oxygen species (ROS) are powerful weapons for various anticancer therapies. However, high glutathione (GSH) levels in cancer cells can significantly reduce the efficacy of such therapies. Methods: In this study, pH-responsive fluorescein-encapsulated zeolitic imidazolate framework-8 nanoparticles were synthesized for ROS-mediated combination therapy. Results: Upon blue light activation, fluorescein displayed a high singlet oxygen photogeneration ability for photodynamic therapy. Concurrently, accumulated Zn2+ from degraded zeolitic imidazolate framework-8 stimulated simultaneous ROS generation and GSH depletion, thereby successfully inducing chemodynamic therapy. This triggered a cascade of photo-physical and chemical processes culminating in the localized generation of ROS, ultimately breaking the intracellular redox equilibrium. Conclusion: This nanoformulation can potentially be used for light-activated ROS-mediated therapy for the management of superficial tumors.

Highly reactive molecules called reactive oxygen species (ROS) are known to be present in excess in cancer cells. As a result, cancer cells are more susceptible to death by any further rise in levels of these species. In the current study, fluorescein-encapsulated zeolitic imidazolate nanoparticles were prepared for blue light-activated ROS-enhancing combination therapy. The nanoparticles displayed significant toxicity against a breast cancer cell line and simultaneously induced glutathione depletion, an antioxidant known to reduce the efficacy of various cancer therapies. Thus, this study reveals the potential of fluorescein-encapsulated zeolitic imidazolate nanoparticles for light-activated ROS-mediated therapy for the treatment of superficial tumors.

Mechanistic interaction studies of synthesized ZIF-8 nanoparticles with bovine serum albumin using spectroscopic and molecular docking approaches.

Numerous studies have shown that nanosized zeolitic imidazolate framework particles (ZIF-8 NPs) serve as promising vehicles for pH-responsive drug delivery. An understanding of their interaction with serum proteins present in physiological systems will thus be of critical importance. In this work, monodisperse ZIF-8 NPs with an average size of 60 nm were synthesized at room temperature and characterized for their various physicochemical properties. Bovine serum albumin (BSA) was used as model serum protein for various interaction studies with ZIF-8 NPs. Spectroscopic techniques such as UV-visible and fluorescence spectroscopy indicated the formation of a ground-state complex with a binding constant of the order 103 M-1 and a single binding site. Steady-state and time-resolved fluorescence spectroscopy confirmed the mechanism of quenching to be static. Conformational changes in the secondary structure of BSA were observed using CD and FT-IR spectroscopies. Binding sites were explored using molecular docking studies.