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Setting-up an In Vitro Model of Rat Blood-brain Barrier BBB: A Focus on BBB Impermeability and Receptor-mediated Transport
Published on: June 28, 2014
Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles
Naroa Serna1, María Virtudes Céspedes2, Paolo Saccardo1
1Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
Engineered protein nanoparticles show enhanced cell penetration but not brain targeting. This study highlights protein engineering for controlled nanoparticle formation, relevant for central nervous system nanomedicine.
Area of Science:
- Biotechnology
- Nanomedicine
- Protein Engineering
Background:
- The low density lipoprotein receptor (LDLR) ligand Seq-1 possesses blood-brain barrier (BBB) crossing activity.
- Protein-only nanoparticles offer potential advantages for drug delivery and biodistribution.
- Targeting the central nervous system (CNS) presents unique bio-physical challenges.
Purpose of the Study:
- To engineer self-assembling protein nanoparticles using Seq-1.
- To evaluate the in vitro cell penetrability and in vivo brain targeting of these nanoparticles.
- To explore protein engineering strategies for controlled nanoparticle formation.
Main Methods:
- Genetic engineering of a single chain polypeptide containing the LDLR ligand Seq-1.
- Characterization of self-assembled 30nm protein-only nanoparticles.
- In vitro assessment of LDLR-dependent cell penetrability.
- Systemic administration and brain targeting evaluation in vivo.
Main Results:
- Successfully created stable, 30nm protein-only nanoparticles from Seq-1.
- Nanoparticulate form significantly enhanced in vitro LDLR-dependent cell penetrability compared to monomers.
- No enhanced brain targeting was observed upon systemic administration.
- Protein engineering, specifically modifying cationic character, promotes controlled oligomerization into functional nanoparticles.
Conclusions:
- While nanoparticle formulation enhances cell penetration, it does not guarantee improved brain targeting due to BBB limitations.
- Protein engineering offers a versatile strategy for creating functional protein nanoparticles.
- This approach is relevant for nanomedicine applications, particularly for CNS-targeted therapies.
