<p>PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity</p>

Abstract

Background: Helper T cell activity is dysregulated in a number of diseases including those associated with rheumatic autoimmunity. Treatment options are limited and usually consist of systemic immune suppression, resulting in undesirable consequences from compromised immunity. Hedgehog (Hh) signaling has been implicated in the activation of T cells and the formation of the immune synapse, but remains understudied in the context of autoimmunity. Modulation of Hh signaling has the potential to enable controlled immunosuppression but a potential therapy has not yet been developed to leverage this opportunity. Methods: In this work, we developed biodegradable nanoparticles to enable targeted delivery of eggmanone (Egm), a specific Hh inhibitor, to CD4 + T cell subsets. We utilized two FDA-approved polymers, poly(lactic-co-glycolic acid) and polyethylene glycol, to generate hydrolytically degradable nanoparticles. Furthermore, we employed maleimide-thiol mediated conjugation chemistry to decorate nanoparticles with anti-CD4 F(ab') antibody fragments to enable targeted delivery of Egm. Results: Our novel delivery system achieved a highly specific association with the majority of CD4 + T cells present among a complex cell population. Additionally, we have demonstrated antigen-specific inhibition of CD4 + T cell responses mediated by nanoparticle-formulated Egm. Conclusion: This work is the first characterization of Egm's immunomodulatory potential. Importantly, this study also suggests the potential benefit of a biodegradable delivery vehicle that is rationally designed for preferential interaction with a specific immune cell subtype for targeted modulation of Hh signaling.

Stable anchoring of bacteria-based protein nanoparticles for surface enhanced cell guidance

“…GFP IB-like pNPs produced by E. coli and L. lactis were covalently attached to maleimide-terminated SAMs through their cysteine aminoacids by means of a Michael addition interfacial reaction using the mCP technique, as recently shown for other nano-objects. [46][47][48] More specifically, the exposed thiol groups of the cysteine residues of GFP at the surface of the pNPs reacted with the maleimide groups of the SAM forming covalent bonds, thus providing a more stable binding in comparison with a simple physisorption procedure (Fig. 1).…”

The interaction between nanoparticles and immune system: application in the treatment of inflammatory diseases

“…Researchers have leveraged polymeric NPs to targeted deliver eggmanone (Egm), a specific Hh inhibitor, to CD4 + T cells via the decoration of anti-CD4 F(ab′) antibody fragments. The novel delivery system targeted CD4 + T cells with high specificity and showed a significant inhibitory effect on CD4 + T cell responses, presented by a reduction of cytokine secretion and helper T cell activation [ 123 ]. Group 2 innate lymphoid cells (ILC2s) are a group of type 2 (T2) inflammatory cells which are implicated in the pathogenesis of asthma [ 124 ].…”

Nanotechnology Against The Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2): Diagnosis, Treatment, Therapy and Future Perspectives

“…Poly (lactic-co-glycolic acid) (PLGA) and PEG are FDA approved polymers which can be employed against COVID-19. This is because of their outstanding biocompatibility and biodegradability when introduced into the human body [ 61–63 ]. Although polymeric nanoparticles are useful tools for drug delivery, they are rapidly taken up by the reticuloendothelial system.…”