ArticleJournal of biomedical science2025
Immune cell uptake of glycinated nanoparticles conjugated to anti-fibrotic peptides enables their prolonged activity and oral administration.
Article in Journal of biomedical science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundFibrosis is a hallmark of various chronic diseases, for which there is no effective cure. Whilst the recombinant form of the human peptide hormone, relaxin (RLX), is being clinically evaluated for its cardioprotective including anti-fibrotic effects in heart failure patients, this is as an injectable which is invasive. This study therefore used biodegradable nanoparticles as a delivery platform to facilitate the prolonged activity and oral application of RLX and a related mimetic as therapeutics.
methodsRLX was conjugated to glycine-functionalised biodegradable superparamagnetic iron oxide nanoparticles (SPION-RLX), enabling therapeutic levels of RLX to be systemically or orally delivered to a murine model of cardiomyopathy. The oral (p.o) application of SPION-RLX was evaluated via daily drinking water (125 ng/5mls/day) from days 7-14 or via oral gavage every 72 h (25 ng/day) from days 14-42 post-injury. The longer-term anti-fibrotic effects of p.o administered SPION-RLX (25 ng/day) or SPION-B7-33 (25 ng/day), a single-chain RLX derivative and relaxin family peptide receptor 1 (RXFP1) agonist were compared to the frontline ACE inhibitor, perindopril (60 ng/day) from days 14-42 post-injury.
resultsSPION-RLX was likely phagocytosed by surveiling RXFP1-expressing dendritic cells (DCs) and transported to the circulation and target site. This allowed for the systemic or oral administration of SPION-RLX to maintain its anti-fibrotic efficacy in mice with cardiomyopathy and restore organ dysfunction after 7 days of treatment. Single-cell transcriptomics provided insights into the phagosomal uptake of SPION-RLX which may have been mediated via scavenger receptors expressed by DCs. When orally administered every 72 h to mice with established cardiomyopathy over a 4 week period, SPION-RLX or SPION-B7-33 demonstrated greater anti-fibrotic efficacy than perindopril.
conclusionThe conjugation of RXFP1-binding peptides to glycine-functionalised biodegradable SPIONs allowed for their circumnavigation of the gut, and prolonged activity as orally administered therapies. These findings have significant ramifications for the oral administration of peptide therapies in general.
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