Poly(<i>N</i>-acryloyl-<scp>l</scp>-phenylalanine) nanoparticles for potential treatment of inflammation in selective organs

Systemic inflammation can lead to multi-organ failure. The existing anti-inflammatory agents show adverse side effects, and the present situation demands new drugs with high therapeutic efficiency. Polymeric nanoparticles based on amino acids could be one of the best alternative solutions due to their cytocompatibility and immune responses. Herein, we synthesized polymeric nanoparticles (Phe NPs) with a size of 20-30 nm using <i>N</i>-acryloyl-L-phenylalanine methyl ester as a precursor. The biological and immune responses of Phe NPs were found to be commanding, which was proven using immune cells (RAW 264.7 macrophages). <i>In vitro</i> study revealed an easy uptake of these NPs (∼98%) by the immune cells and that they can reduce inflammation by improving the immune response. <i>In silico</i> molecular docking results revealed that Phe NPs could potentially interact with immune cytokines such as IL-6, NF-κβ, TNF-α, COX2 and IL-1β. Phe NPs exhibit a similar type of binding and interaction as ibuprofen (IBF), which confirms its immune response to control inflammation. The anti-inflammatory response of Phe NPs was established through an <i>in vitro</i> inflammation model developed using LPS-stimulated RAW 264.7 macrophages. Furthermore, an LPS-induced <i>in vivo</i> rat model was developed, which revealed that Phe NPs are useful for the treatment of systemic inflammation. Blood-based biochemical parameters such as C-reactive protein, lactate and procalcitonin levels were determined, and the anti-inflammatory responses of Phe NPs were confirmed through RT-PCR analysis by measuring the levels of inflammatory markers such as TNF-α, IL-6 and VEGF. Finally, an <i>in vivo</i> systemic inflammation rat model was used to examine the systemic organs (brain, liver, kidneys, spleen, lungs and heart) before and after treatment with Phe NPs to prove their anti-inflammatory responses. H&E histological analysis of different organs further revealed that even at a low dose of 100 μg kg^-1, Phe NPs are immune-responsive/protective and anti-inflammatory in nature.