Description of science

DLVR’s innovative technology is based on the synthesis and use of an HDL-mimetic phospholipid-based nanoparticle called HPPS (HDL-like Peptide-Phospholipid Scaffold). Exploiting the property of HDL to create a hydrophobic channel in the cell membrane, HPPS delivers its payload directly into the cytosol of its target cells. It further mimics the natural targeting of HDL to the scavenger receptor class B type I (SR-BI) which is upregulated in selected cancers, ocular and steroidogenic tissues, and the liver. HPPS exhibits similar pharmacokinetics as plasma-derived HDL with a long stable circulating time and favourable biodistribution. HPPS nanoparticles are ultra-small (10-25 nm), nontoxic, nonimmunogenic, biocompatible, easy to synthesize and customizable.

 

HPPS closely resembles the structure of plasma-derived spherical high-density lipoprotein (HDL) by replacing apoA-I protein with self-assembled apoA-I mimetic peptides on the phospholipid monolayer of the nanoparticle.  The phospholipid monolayer is distinct from the more common phospholipid bilayer liposome structure.  This results in amphipathic nanoparticles that are well-controlled and retain the HDL-like capacity for long circulation times and effective transport of lipophilic payloads.

 

HPPS nanoparticles can be customized to carry different types and sizes of payloads, which can include: chemotherapeutics, small bioactive molecules, photodynamic therapy agents, and contrast agents.  Different targeting moieties (small molecules, antibodies, aptamers, peptides, and targeting nucleotide sequences) can be linked to the surface of the nanoparticle to direct the payload to the intended target tissue.

 

Summary of the Key Differentiators and Benefits of the HPPS nanoparticle:

  • Tumour targeting/penetration
    • delivery mediated by SR-B1 receptor
    • direct cytosolic delivery avoids degradation by endocytosis
  • Safety and reduced toxicity
    • biocompatible, non-immunogenic
    • apoA-1 mimetic, ultra small, stable in plasma
  • Enhanced therapeutic effect
    • payload shielding
    • RNA knockdown