CriPec® actively targeted nanoparticles (CriPec ATN) represents the combination of the CriPec platform with targeting ligands. Modification of the surface of the CriPec nanoparticles with these ligands further increases target cell interaction, thereby additionally enhancing therapeutic effects whilst reducing off-target toxicity.
Assembly of the CriPec ATN nanoparticles
The assembly of CriPec ATN starts with the two-step process characteristic for the CriPec nanomedicines in general:
- Derivatisation of a drug molecule with a target-selective linker.
- For CriPec ATN, a mixture between azide-CriPec polymer and CriPec polymer are used.
- The CriPec polymers self-assemble together with the drug-linker into polymeric micelles.
- Crosslinking of both the CriPec polymer and the drug-linker results in transiently stable nanoparticles, with a selected number of azide groups presented on the surface.
- The nanoparticles are purified in a single purification step.
- Chemical coupling of a selected ligand to the azide-presenting CriPec ATN is achieved in a one-step reaction.
- A straightforward purification protocol yields highly pure CriPec ATN as final drug product.
Ligand selection is based on the target tissue and cell characteristics, and aims to achieve the highest specificity, most selective binding and cellular internalisation. Potential ligands comprise antibodies, antibody fragments, peptides or other small molecular weight compounds.
Unique features CriPec ATN
The combination of CriPec nanomedicines with ligands results in actively targeted nanoparticles with additional valuable features as the advantages of nanoparticulate systems are combined with beneficial features of antibody targeting:
- Straightforward chemistry
- Very selective conjugation of a ligand with high conversion
- More than 1 ligand per nanoparticle possible
- Higher cellular/tissue selectivity resulting in an increased intracellular drug concentration
- Synergistic efficacy with entrapped drug(s) in case of intrinsically active ligand(s)