Poly(lactic acid) nanoparticles labeled with biologically active Neutravidin for active targeting

Area of Science:

• Biomaterials Science
• Nanotechnology
• Surface Chemistry

Background:

• Poly(DL-lactic acid) (PLA) nanoparticles are versatile drug delivery vehicles.
• Attaching targeting ligands to nanoparticles enhances therapeutic efficacy.
• NeutrAvidin offers a robust platform for biotin-based conjugation.

Purpose of the Study:

• To covalently immobilize NeutrAvidin onto the surface of PLA nanoparticles.
• To characterize the NeutrAvidin-labeled nanoparticles for size, protein concentration, and binding capacity.
• To assess the potential of these nanoparticles for active targeting applications.

Main Methods:

• Introduction of sulfhydryl groups onto PLA nanoparticles via carbodiimide chemistry.
• Conjugation of NeutrAvidin to thiolated nanoparticles using a bifunctional cross-linker.
• Quantification of surface thiol groups and bound NeutrAvidin.
• Evaluation of particle size, protein concentration, and biotin binding activity.

Main Results:

• Surface thiol concentration was determined to be 105 +/- 15 mmol/mol PLA.
• Significant amounts of NeutrAvidin were covalently bound, with controllable concentrations up to 6 mmol/mol PLA.
• NeutrAvidin-labeled nanoparticles retained biotin-binding capacity, although activity was reduced due to aggregation.
• PLA nanoparticles functionalized with NeutrAvidin show promise for biotinylated antibody-based active targeting.

Conclusions:

• PLA nanoparticles can be effectively functionalized with NeutrAvidin via surface thiol modification.
• The NeutrAvidin-PLA nanoparticle system demonstrates potential for two-step active targeting strategies.
• Further optimization may be needed to mitigate NeutrAvidin aggregation and enhance activity for therapeutic applications.