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The polyplex, protein corona, cell interplay: Tips and drawbacks.

Daniele Maiolo1, Jessica Colombo2, Jennifer Beretta2

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Polyplexes (PX) show different biological behavior despite similar physicochemical properties. Their protein corona significantly influences gene delivery efficiency and toxicity, highlighting the importance of the biological environment.

Keywords:
Bio-nano interactionCell transfectionPolyplexProtein coronaSelf-assembly

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Area of Science:

  • Biomaterials Science
  • Gene Delivery Systems
  • Nanomedicine

Background:

  • Polyplexes (PX), formed by polycations and nucleic acids, are key in gene delivery.
  • The protein corona of PX, biomolecules adsorbed onto their surface in biological fluids, is an understudied factor influencing their performance.
  • Linear and branched polyethylenimines (lPEI and bPEI) are widely used non-viral gene vectors.

Purpose of the Study:

  • To investigate the physicochemical properties and protein corona of DNA complexes with lPEI and bPEI.
  • To correlate these properties with the toxicity and transfection efficiency of the polyplexes.
  • To understand how the biological milieu affects polyplex behavior and gene delivery.

Main Methods:

  • Synthesis and characterization of polyplexes using linear and branched polyethylenimines with DNA.
  • Analysis of physicochemical properties (e.g., size, stability) of the polyplexes.
  • Evaluation of protein corona formation and its impact on cellular toxicity and transfection efficiency.

Main Results:

  • lPEI-DNA and bPEI-DNA complexes exhibited similar physicochemical characteristics.
  • Despite similarities, significant differences were observed in their biological behavior, including toxicity and transfection efficiency.
  • The biological environment was found to greatly influence polyplex size, stability, and gene delivery capabilities.

Conclusions:

  • Protein corona formation and the biological milieu are critical, often overlooked, parameters in polyplex-mediated gene delivery.
  • Structure-activity relationships in polyplexes are complex and highly dependent on environmental interactions.
  • Methodologies developed can aid in interpreting polyplex behavior and designing improved gene delivery systems.