Protein delivery into cells using inorganic nanoparticle–protein supramolecular assemblies

Protein delivery holds enormous promise for therapeutic applications.1 Proteins can be used to introduce deficient proteins due to genetic defects or therapeutic proteins to ameliorate other disease states.2 To date, protein delivery strategies have focused primarily on extracellular targets, and are effective for delivery of proteins that have external receptors or endogenous mechanisms for cellular internalization

Federica Scaletti

2018

Scholarcy highlights

  • Protein delivery holds enormous promise for therapeutic applications.1 Proteins can be used to introduce deficient proteins due to genetic defects or therapeutic proteins to ameliorate other disease states.2 To date, protein delivery strategies have focused primarily on extracellular targets, and are effective for delivery of proteins that have external receptors or endogenous mechanisms for cellular internalization
  • Most nanoparticle-protein supramolecular assemblies are uptaken by cells via endocytic mechanism and are subsequently released into the cytosol through endosomal escape
  • Recent studies by Tang et al have demonstrated the use of Nanoparticle-stabilized capsules as efficient, versatile delivery vehicles for direct cytosolic delivery of proteins such as Green fluoresecent protein.19
  • Through the combined effect of electrostatic interaction between the positively-charged ligand and the cell membrane, and the lipophilic nature of the oil core, these NPSCs are capable of cytosolic delivery of their protein cargo through membrane fusion
  • To NPSCs, these supramolecular assemblies fused with cell membranes through interaction of Arg-NPs ligands with the membrane, releasing the Etagged protein directly into the cytosol, bypassing endosomal entrapment
  • Chertok et al reported the use of an external magnetic field as a targeting methodology for selective delivery of protein drug-loaded magnetic particles to brain tumors
  • The overall structure of these vectors can be modulated to allow insertion of imaging or targeting modules, or to incorporate a hydrophobic core for lipophilic molecule loading or facilitating uptake

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