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<p>Diabetic nephropathy (DN), a progressive microvascular complication of diabetes, is primarily driven by chronic hyperglycemia-induced inflammation, fibrosis, and cell cycle dysregulation. Recent studies identified mitotic arrest deficient 2-like protein B (MAD2B) as a critical regulatory protein in DN, markedly upregulated in high-glucose-treated human glomerular mesangial cells (HGMCs), accompanied by a 2.8-fold increase in IL-6 expression, highlighting its pathological relevance. To achieve targeted therapy and real-time monitoring, we designed a silica-based hybrid nanoplatform incorporating a lanthanide coordination polymer [Sm(L)₃·CH₃OH] (CP1) with a well-defined tricapped trigonal prismatic geometry (confirmed by SCXRD). CP1 was loaded with a lipophilic bioactive molecule—Compound 1, a diterpenoid quinone derived from <i>Salvia miltiorrhiza</i> known for anti-inflammatory and anti-fibrotic properties—and subsequently coated with carboxymethyl chitosan (CMCS) and 3-aminopropyltrimethoxysilane (APTMS) to yield CMCS-APTMS@CP1@1. The resulting nanoplatform exhibited enhanced aqueous stability, biocompatibility, and sustained-release capability under physiological conditions. Notably, CMCS-APTMS@CP1@1 also demonstrated robust fluorescence responsiveness toward MAD2B, enabling sensitive detection with a linear response in the 0–40&#xa0;μM range (R<sup>2</sup> = 0.998) and a detection limit of 58&#xa0;nM. Fluorescence lifetime and UV–vis analyses revealed a Förster resonance energy transfer (FRET)-mediated quenching–recovery mechanism. Molecular docking confirmed strong hydrogen bonding (∼1.7&#xa0;Å) between the imide moiety of the Sm complex and the hydroxyl group of TYR-280 in MAD2B. These findings underscore the dual functionality of CMCS-APTMS@CP1@1 as both a smart therapeutic carrier and a MAD2B-responsive fluorescence probe, offering promising potential for precision DN treatment and monitoring.</p>

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Silica Nanoplatform with Bioactive Molecule Detection and Delivery for Diabetic Nephropathy Therapy

  • 期刊论文

  • 发表日期：

    2025年8月13日

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  • Yaguang Zhang,
  • Mingyan Zhou,
  • Xiaoyu Zhao

摘要

Diabetic nephropathy (DN), a progressive microvascular complication of diabetes, is primarily driven by chronic hyperglycemia-induced inflammation, fibrosis, and cell cycle dysregulation. Recent studies identified mitotic arrest deficient 2-like protein B (MAD2B) as a critical regulatory protein in DN, markedly upregulated in high-glucose-treated human glomerular mesangial cells (HGMCs), accompanied by a 2.8-fold increase in IL-6 expression, highlighting its pathological relevance. To achieve targeted therapy and real-time monitoring, we designed a silica-based hybrid nanoplatform incorporating a lanthanide coordination polymer [Sm(L)₃·CH₃OH] (CP1) with a well-defined tricapped trigonal prismatic geometry (confirmed by SCXRD). CP1 was loaded with a lipophilic bioactive molecule—Compound 1, a diterpenoid quinone derived from Salvia miltiorrhiza known for anti-inflammatory and anti-fibrotic properties—and subsequently coated with carboxymethyl chitosan (CMCS) and 3-aminopropyltrimethoxysilane (APTMS) to yield CMCS-APTMS@CP1@1. The resulting nanoplatform exhibited enhanced aqueous stability, biocompatibility, and sustained-release capability under physiological conditions. Notably, CMCS-APTMS@CP1@1 also demonstrated robust fluorescence responsiveness toward MAD2B, enabling sensitive detection with a linear response in the 0–40 μM range (R2 = 0.998) and a detection limit of 58 nM. Fluorescence lifetime and UV–vis analyses revealed a Förster resonance energy transfer (FRET)-mediated quenching–recovery mechanism. Molecular docking confirmed strong hydrogen bonding (∼1.7 Å) between the imide moiety of the Sm complex and the hydroxyl group of TYR-280 in MAD2B. These findings underscore the dual functionality of CMCS-APTMS@CP1@1 as both a smart therapeutic carrier and a MAD2B-responsive fluorescence probe, offering promising potential for precision DN treatment and monitoring.