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  4. Growth factor choice is critical for successful functionalization of nanoparticles

Growth factor choice is critical for successful functionalization of nanoparticles

Frontiers in Neuroscience, 2015 · DOI: 10.3389/fnins.2015.00305 · Published: September 2, 2015

PharmacologyNeurologyBiomedical

Simple Explanation

Nanoparticles can be used to help the nervous system regenerate. To do this, they need to be functionalized with molecules that have biological functions. This study looks at using nerve growth factor (NGF) and glial cell-line derived neurotrophic factor (GDNF) to functionalize nanoparticles. The study found that the way these growth factors are attached to the nanoparticles is very important. Covalently binding NGF impaired its bio-functionality, while non-covalent binding was successful. Non-covalent binding of GDNF showed initial bio-functionality but was unstable. The study highlights that it's important to check if functionalized growth factors are biologically active and stably bound using suitable biological models, as successful functionalization depends on the binding chemistry used and can be hard to predict.

Study Duration
Not specified
Participants
Rat pheochromocytoma cell line (PC12) and neonatal rats (postnatal day 4)
Evidence Level
In vitro and ex vivo study

Key Findings

  • 1
    Covalent binding of NGF to PEI-NPs impaired its bio-functionality, while non-covalent binding successfully differentiated PC12 cells.
  • 2
    Non-covalent binding of GDNF to PEI-NPs showed initial bio-functionality but turned out to be unstable in conjugation.
  • 3
    Successful functionalization of magnetic NPs with growth factors depends on the used binding chemistry and is hardly predictable.

Research Summary

This study investigates the functionalization of nanoparticles (NPs) with nerve growth factor (NGF) and glial cell-line derived neurotrophic factor (GDNF) to support regeneration in the nervous system. The study found that covalent binding of NGF to PEI-NPs impaired its bio-functionality, while non-covalent binding differentiated PC12 cells reliably. Non-covalent binding of GDNF showed a satisfying bio-functionality but was unstable in conjugation to the PEI-NPs. The research emphasizes the importance of assessing bio-functionality and binding stability of functionalized growth factors using proper biological models, as successful functionalization depends on the used binding chemistry and is hardly predictable.

Practical Implications

Therapeutic Development

Functionalization strategies for magnetic nanoparticles used as therapeutics have to be reproducible.

Binding Chemistry Selection

Growth factor bio-functionality can be impaired by covalent binding to nanoparticles, indicating the importance of choosing the correct binding chemistry.

Bio-functionality Assessment

It's important to check the bio-functionality of growth factors bound to NPs with a proper biological model.

Study Limitations

  • 1
    The exact binding site in the structure of the protein is somehow random, the outcome regarding the bio-functionality seems to be random as well.
  • 2
    Different serum content in the media of PC12 cells and organotypic spinal cord cultures is a problem for using non-covalent approaches.
  • 3
    Serum proteins and GDNF appear to compete for binding, which results in a loss of GDNF bound to PEI-NPs.

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