Methotraxate-Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE−/− Mice

Cinzia Stigliano, Maricela R. Ramirez, Jaykrishna V. Singh, Santosh Aryal, Jaehong Key, Elvin Blanco, Paolo Decuzzi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Atherosclerosis is an inflammatory disorder characterized by the progressive thickening of blood vessel walls eventually resulting in acute vascular syndromes. Here, intravenously injectable hybrid nanoconstructs are synthesized for tempering immune cell inflammation locally and systemically. Lipid and polymer chains are nanoprecipitated to form 100 nm spherical polymeric nanoconstructs (SPNs), loaded with methotrexate (MTX) and subsequently labeled with Cu64 and fluorescent probes for combined nuclear/optical imaging. Upon engulfment into macrophages, MTX SPNs intracellularly release their anti-inflammatory cargo significantly lowering the production of proinflammatory cytokine (interleukin 6 and tumor necrosis factor α) already at 0.06 mg mL−1 of MTX. In ApoE−/− mice, fed with high-fat diet up to 17 weeks, nuclear and optical imaging demonstrates specific accumulation of SPNs within lipid-rich plaques along the arterial tree. Histological analyses confirm SPN uptake into macrophages residing within atherosclerotic plaques. A 4-week treatment with biweekly administration of MTX SPNs is sufficient to reduce the plaque burden in ApoE−/− mice by 50%, kept on high-fat diet for 10 weeks. Systemic delivery of MTX to macrophages via multifunctional, hybrid nanoconstructs constitutes an effective strategy to inhibit atherosclerosis progression and induce, potentially, the resorption of vascular lesions.

Original languageEnglish
Article number1601286
JournalAdvanced healthcare materials
Volume6
Issue number13
DOIs
Publication statusPublished - 2017 Jul 5

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Macrophages
Apolipoproteins E
Methotrexate
Blood Vessels
Atherosclerosis
Nutrition
Oils and fats
Lipids
Optical Imaging
Imaging techniques
High Fat Diet
Blood vessels
Tempering
Fats
Atherosclerotic Plaques
Fluorescent Dyes
Polymers
Interleukin-6
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

Cite this

Stigliano, Cinzia ; Ramirez, Maricela R. ; Singh, Jaykrishna V. ; Aryal, Santosh ; Key, Jaehong ; Blanco, Elvin ; Decuzzi, Paolo. / Methotraxate-Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE−/− Mice. In: Advanced healthcare materials. 2017 ; Vol. 6, No. 13.
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Methotraxate-Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE−/− Mice. / Stigliano, Cinzia; Ramirez, Maricela R.; Singh, Jaykrishna V.; Aryal, Santosh; Key, Jaehong; Blanco, Elvin; Decuzzi, Paolo.

In: Advanced healthcare materials, Vol. 6, No. 13, 1601286, 05.07.2017.

Research output: Contribution to journalArticle

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