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Background <p>The theranostic application of epirubicin (EPI) and superparamagnetic iron oxide nanoparticles (SPIONs) represents a promising strategy for cancer treatment, combining the therapeutic efficacy of EPI with the diagnostic and targeted delivery capabilities of SPIONs.</p> Methodology <p>In this study, EPI and SPIONs were co-encapsulated within poly (lactic-co-glycolic acid)-block-poly (ethylene glycol) (PLGA-PEG) using a water-in-oil-in-water (W<sub>1</sub>/O/W<sub>2</sub>) double emulsion system. The physicochemical characterization of the resulting EPI/SPIONs-loaded PLGA-PEG nanoparticles (NPs) was conducted, focusing on size distribution, magnetic properties, EPI loading content, and release rate. Pharmacokinetic studies, histopathological examinations, fluorescence analyses, and magnetic resonance imaging (MRI) analyses were performed on New Zealand White rabbits and Sprague-Dawley injected intravenously rats.</p> Results <p>SPIONs and NPs exhibited Z-average diameters of 27&#xa0;nm and 196&#xa0;nm, respectively, with polydispersity indices (PIs) of 0.050 and 0.105. The NP formulation demonstrated a saturation magnetization of 1.6 emu/g. NPs released approximately 40% of EPI at pH 5.5, significantly higher than at pH 7.4, which remained below 10%. NPs enhanced EPI cytotoxicity in C6 glioma cells while reducing it in NIH/3T3 fibroblast cells. Fluorescence imaging revealed substantial EPI accumulation in NP-injected rabbits’ hepatic and renal tissues. Similarly, NP-injected rats exhibited strong negative contrast in T<sub>2</sub>-weighted MRI of these tissues. Histopathological analysis indicated differential myocardial protection in NP-injected rabbits. NPs prolonged EPI’s serum half-life from 4.5&#xa0;h to 25.5&#xa0;h.</p> Conclusion <p>NPs successfully achieved targeted accumulation of SPIONs and EPI in hepatic and renal tissues while sparing myocardial tissue. The NPs exhibited a differential EPI intracellular release profile for EPI, highlighting their potential for targeted elimination of cancer cells using external magnetic fields.</p>

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Theranostic potential and safety assessment of epirubicin-loaded SPIONs/PLGA-PEG nanoparticles in rabbit

  • 期刊论文

  • 发表日期：

    2025年7月17日

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  • Hossein Kamali,
  • Zahra Jafari,
  • Manouchehr Teymouri,
  • Hanieh Rezaee,
  • Elnaz Khordad,
  • Jafar Mosafer

摘要

Background

The theranostic application of epirubicin (EPI) and superparamagnetic iron oxide nanoparticles (SPIONs) represents a promising strategy for cancer treatment, combining the therapeutic efficacy of EPI with the diagnostic and targeted delivery capabilities of SPIONs.

Methodology

In this study, EPI and SPIONs were co-encapsulated within poly (lactic-co-glycolic acid)-block-poly (ethylene glycol) (PLGA-PEG) using a water-in-oil-in-water (W1/O/W2) double emulsion system. The physicochemical characterization of the resulting EPI/SPIONs-loaded PLGA-PEG nanoparticles (NPs) was conducted, focusing on size distribution, magnetic properties, EPI loading content, and release rate. Pharmacokinetic studies, histopathological examinations, fluorescence analyses, and magnetic resonance imaging (MRI) analyses were performed on New Zealand White rabbits and Sprague-Dawley injected intravenously rats.

Results

SPIONs and NPs exhibited Z-average diameters of 27 nm and 196 nm, respectively, with polydispersity indices (PIs) of 0.050 and 0.105. The NP formulation demonstrated a saturation magnetization of 1.6 emu/g. NPs released approximately 40% of EPI at pH 5.5, significantly higher than at pH 7.4, which remained below 10%. NPs enhanced EPI cytotoxicity in C6 glioma cells while reducing it in NIH/3T3 fibroblast cells. Fluorescence imaging revealed substantial EPI accumulation in NP-injected rabbits’ hepatic and renal tissues. Similarly, NP-injected rats exhibited strong negative contrast in T2-weighted MRI of these tissues. Histopathological analysis indicated differential myocardial protection in NP-injected rabbits. NPs prolonged EPI’s serum half-life from 4.5 h to 25.5 h.

Conclusion

NPs successfully achieved targeted accumulation of SPIONs and EPI in hepatic and renal tissues while sparing myocardial tissue. The NPs exhibited a differential EPI intracellular release profile for EPI, highlighting their potential for targeted elimination of cancer cells using external magnetic fields.