ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Nanobiotechnology
Bioengineered Exosome-mRNA Hybrids: A Breakthrough in Targeted miRNA Delivery for Diabetic Kidney Fibrosis Therapy
Provisionally accepted
- Ezhou Central Hospital, Ezhou, China
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Diabetic nephropathy (DN) is driven in part by progressive podocyte injury, yet actionable upstream regulators and precise delivery strategies remain limited. Here, we systematically investigated the role of poly(ADP-ribose) polymerase 1 (PARP1) in hyperglycemia-induced podocyte damage and developed a biomimetic, podocyte-targeted siRNA delivery system to silence PARP1. Transcriptomic profiling of MPC5 podocytes exposed to high glucose identified PARP1 as a prominently upregulated hub associated with activation of the TGF-β/Smads axis. Pharmacological inhibition with PJ-34 and gene silencing attenuated TGF-β/Smads signaling, restored autophagic flux, and reduced inflammatory responses, apoptosis, and profibrotic changes in vitro, and alleviated glomerular injury in a streptozotocin-induced type 1 diabetic mouse model. To enable cell-specific RNA interference, we engineered PLGA-core nanoparticles loaded with PARP1 siRNA and coated them with red blood cell membrane (RBCm) for immune evasion, further functionalizing the surface with the podocyte-targeting ligand BMS-α. The nanosystem exhibited robust siRNA loading into the PLGA core and favorable physicochemical stability, while BMS-α markedly enhanced podocyte targeting via MC-1R–related uptake, supported by antibody-blocking and colocalization approaches. In diabetic mice, siPARP1-NPs@RBCm-BMS-α improved podocyte integrity and glomerular structure and ameliorated renal dysfunction. Collectively, these findings establish PARP1 as a mechanistically important driver of DN-associated podocyte injury and propose a biomimetic, receptor-relevant targeted siRNA platform as a promising, translatable strategy for precision intervention in DN.
Keywords: Biomimetic Red Blood Cell Membrane, diabetic nephropathy, Podocyte Targeting, Poly(ADP-Ribose) polymerase 1, Small interfering RNA delivery, TGFβ/Smads pathway
Received: 20 Sep 2025; Accepted: 28 Jan 2026.
Copyright: © 2026 Ke, Cao, Zhang and Xing. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jing Ke
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