Lupus nephritis (LN) is a prevalent complication of systemic lupus erythematosus (SLE) [1]. It characterised by glomerular accumulation of immune complexes and a surge in circulating cell-free DNA (cfDNA), which contribute to irritation and ensuing renal impairment [2]. A wide range of remedies, together with corticosteroids, immunosuppressive brokers, and biologics, have been deployed to fight this situation [3], [4], [5]. Notably, transplantation therapies using mesenchymal stromal cells (MSCs) have emerged as notably advantageous, owing to their capability to modulate the immune system and facilitate tissue regeneration [6], [7]. Nonetheless, the efficacy of present stem cell therapies, usually delivered by way of systemic injections, is hampered by an absence of concentrating on precision and speedy clearance by the physique’s immune system, typically necessitating a number of administrations. Whereas the nanoencapsulation of MSCs inside cytoprotective semipermeable shells has demonstrated potential in enhancing cell viability, therapeutic efficacy, and dampening immune reactions, there stays a essential want for additional refinement to beat obstacles pertaining to security, useful adaptability, and sustained presence on the supposed website [8], [9]. Thus, there’s a urgent want for superior engineered MSCs that may particularly goal the affected renal tissues and supply efficient immune regulation to deal with LN.
Right here, we suggest a biomimetic strategy involving polydopamine (PDA)-mediated encapsulation of MSCs with dendritic polylysine nanogels for focused remedy of LN, as schemed in Fig. 1. PDA is a bioinspired polymer derived from mussel adhesive secretions [10], [11]. In response to its distinctive biocompatibility and adhesive properties, PDA has discovered intensive functions throughout varied biomedical and engineering fields [12], [13], [14], [15]. For instance, cells coated with PDA when immersed in a dopamine answer exhibit improved stability, biocompatibility, and viability [16], [17], [18]. Apart from, the PDA layer serves as a flexible platform for subsequent useful enhancements, together with augmented concentrating on precision and therapeutic effectiveness [19], [20], [21]. However, dendritic polylysine nanogels, with their ample lively websites, are well-suited for integration with PDA [22], [23], [24]. Moreover, these nanogels are notably adept at binding the elevated ranges of cell-free DNA (cfDNA) discovered within the kidneys affected by lupus nephritis (LN), indicating a robust potential for focused renal remedy [25], [26]. Subsequently, by combining PDA and dendritic polylysine nanogels on MSC surfaces, we envision the event of an revolutionary cell supply system with the potential to reinforce LN remedy.
On this research, we offered biomimetic engineered MSCs with PDA and dendritic polylysine-based nanogel coating for superior cell-targeted remedy to deal with LN. The preliminary MSCs had been immersed in a dopamine answer to kind the primary PDA layer, adopted by the creation of a second encapsulation layer utilizing dithio-bis-(succinimidyl propionate) (DSP) to crosslink three-generation poly-lysine dendrimer (G3K) precursors. Primarily based on the Michael addition response between the amino teams on polylysine and the quinones on the PDA layer, the nanogel can bind to the PDA-coated phospholipid bilayer with desired stability and sturdiness. As well as, it was effectively demonstrated that the PDA/nanogel-coated (PNC) MSCs might considerably improve cell bioactivity and enhance the immunomodulatory perform. Notably, upon intravenous injection into MLR/lpr mice, the PNC-MSCs displayed enhanced recruitment and extended retention on the affected renal website. This focused accumulation enabled the encapsulated MSCs to exert their immunomodulatory results and alleviate the development of LN. These findings signify an enhanced software of cell nanoencapsulation and underscore the potential worth of PNC-MSCs as a promising therapeutic strategy for treating LN.
