Title : Liposomal encapsulation of silver nanoparticles suppresses nanoparticle-induced ROS and inflammation, and induces caspase-dependent apoptosis
Abstract:
High concentrations of silver nanoparticles (AgNP) are increasingly present as active ingredient in everyday consumable products for antibacterial purposes causing increased human exposure and high risk of adverse effect development. In this study, AgNP were encapsulated dipalmitoylphosphatyidyl choline (DPPC) based liposome, to enhance intracellular delivery, associated cytotoxicity and suppress AgNP induced inflammation. It was noted that as a result of the encapsulation, 0.625 µg/ml liposomal-AgNP (Lipo-AgNP) at induced significant cell death in THP1 cell lines at a notably lower dose than that of the uncoated AgNP induced cytotoxicity. The induced cytotoxicity was shown to result in an increased level of DNA fragmentation resulting in a cell cycle interruption at the S phase of the cell cycle. The predominate form of cell death upon exposure to both uncoated and Lipo-AgNP was found to be caspase dependent and ROS independent apoptosis.
In THP1 monocytes and THP1 differentiated macrophages (TDM), it was found that AgNP induced release of IL-1β. IL-6, IL-8 and TNF-α in THP1 monocytes all of which were suppressed by Lipo-AgNP exposure. AgNP was also found to induce release of IL-1β, IL-6 and TNF-α in TDMs while Lipo-AgNP suppressed these cytokine releases. However, both AgNP and Lipo-AgNP suppressed IL-1β and TNF-α release in LPS-stimulated THP1 monocytes and TDM respectively. Lastly, we showed that AgNP may induce uncontrolled inflammation through induction of STAT3 protein expression in LPS stimulated THP1 monocytes and TDMs whether they are stimulated with LPS or not. This data showed that Lipo-AgNP suppressed AgNP induced inflammation and thus Lipo-AgNP may be particularly useful in treatment of bacteria induced inflammatory diseases.
These findings showed that encapsulation of AgNP enhance AgNP cytotoxicity and mediates a ROS-independent induction of apoptosis.in addition, Lipo-AgNP suppressed AgNP induced inflammation which may be linked to the suppressed ROS. this immunosuppression may be important in application of Lipo-AgNP in treatment of inflammatory diseases like Crohn’s disease, ulcerative colitis and inflammatory breast cancer.
Audience take away:
• Encapsulation of AgNP in liposome can be carried out by a cost-effective method through extrusion.
• Encapsulation of AgNP in liposome help enhance intracellular delivery of AgNP into cancer cell without induction of ROS
• The encapsulation also aids suppression of associated inflammatory response due to AgNP exposure
• Encapsulation of AgNP is a potential therapeutic strategy for treatment of inflammatory diseases Explain how the audience will be able to use what they learn?
