Boosted transport of Theranostic Angiopep-2 engineered crosslinked Hyaluronic Acid NanoParticles (Thera-ANG-cHANPs) in glioblastoma cells

Angiopep-2 is a 19 amino acid synthetic peptide that demonstrated the ability to shuttle active agents across the BBB in clinics by the interaction with LRP-1 receptors. The combination of such peptide with properly designed drug delivery systems can strongly improve the outcome of patients with brain tumours, a pathology in which the standard of care is scarcely effective because of poor transport and resistance. In this work, we engineered theranostic crosslinked hyaluronic acid nanoparticles (Thera-cHANPs), co-encapsulating Gd-DTPA with boosted relaxivity and the chemotherapeutic drug Irinotecan (CPT-11), with Angiopep-2, to produce Thera-ANG-cHANPs. Thera-ANG-cHANPs demonstrated stability in the biological environment, boosted uptake by patient derived Glioblastoma cells and, as consequence of improved transport, a boosted therapeutic effect exerted with a lower dose of drug in a reduced time window.