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Bioinspired Oligo-Urethane Nanoparticles for Delivering Exogenous C-Type Natriuretic Peptide: Synthetic Biomaterial Nanocarrier Complexes and Their Interactions with Cardiac Myofibroblasts.
Siqueira, Nataly M; Chung, Shirley; Shrestha, Suja; Zhong, Aileen; Caruso, Laura-Lee; Mirani, Bahram; Mirzaei, Zahra; Simmons, Craig A; Santerre, J Paul.
Afiliación
  • Siqueira NM; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
  • Chung S; Translational Biology and Engineering Program and Ted Rogers Centre for Heart Research, Toronto, Ontario M5G 1M1, Canada.
  • Shrestha S; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
  • Zhong A; Translational Biology and Engineering Program and Ted Rogers Centre for Heart Research, Toronto, Ontario M5G 1M1, Canada.
  • Caruso LL; Translational Biology and Engineering Program and Ted Rogers Centre for Heart Research, Toronto, Ontario M5G 1M1, Canada.
  • Mirani B; Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada.
  • Mirzaei Z; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
  • Simmons CA; Translational Biology and Engineering Program and Ted Rogers Centre for Heart Research, Toronto, Ontario M5G 1M1, Canada.
  • Santerre JP; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
Biomacromolecules ; 24(7): 3149-3158, 2023 07 10.
Article en En | MEDLINE | ID: mdl-37344353
In a healthy heart, cells naturally secrete C-type natriuretic peptide (CNP), a cytokine that protects against myofibroblast differentiation of cardiac fibroblasts and extracellular matrix deposition leading to fibrosis. CNP availability during myocardial remodeling is important to prevent cardiac fibrosis, but CNP is limited after an injury because of the loss of cardiomyocytes and the activation of cardiac fibroblasts to myofibroblasts. We hypothesized that the sustained release of exogenous CNP from oligo-urethane nanoparticles (NPs) would reduce differentiation of human cardiac fibroblasts toward a myofibrogenic phenotype. Our work used a modified form of a degradable polar hydrophobic ionic (D-PHI) oligo-urethane, which has shown the ability to self-assemble into NPs for the delivery of peptide and oligonucleotide biomolecules. The CNP-loaded NPs (NPCNP) were characterized for a diameter of 129 ± 1.4 nm and a ζ potential of -46 ± 7.8 mV. Treatment of cardiac fibroblasts with NPCNP increased cyclic guanosine-monophosphate (cGMP) synthesis, confirming that exogenous CNP delivered via oligo-urethane NPs is bioactive and can induce downstream signaling that has been implicated in antagonizing transforming growth factor-ß1 (TGF-ß1)-induced myofibrogenic differentiation. It is also shown that treatment with NPCNP attenuated contraction of collagen gels by cardiac myofibroblasts stimulated with TGF-ß1. Coating with heparin on the NPCNP (HEP-NPCNP) exemplified an approach to extend the release of CNP from the NPs. Both HEP-NPCNP and NPCNP show minimal cell toxicity, studied up to 0.25 × 1010 NPs/mL in culture media. These findings support further investigation of CNP delivery via NPs as a future therapy for suppressing cardiac fibrosis.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta1 / Miofibroblastos Límite: Humans Idioma: En Revista: Biomacromolecules Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta1 / Miofibroblastos Límite: Humans Idioma: En Revista: Biomacromolecules Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos