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 journalArticlepeer-review

30 Citations (Scopus)


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
Issue number13
Publication statusPublished - 2017 Jul 5

Bibliographical note

Funding Information:
The authors acknowledge support from the “George and Angelina Kostas Research Center for Cardiovascular Nanomedicine” at the Houston Methodist Research Institute, Houston (TX, USA). P.D. acknowledges partial support from the Italian Government through the Italian Institute of Technology (IIT) in Genova.

Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science


Dive into the research topics of 'Methotraxate-Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE−/− Mice'. Together they form a unique fingerprint.

Cite this