Improving Bioavailability of Hydrophobic Prodrugs through Supramolecular Nanocarriers Based on Recombinant Proteins for Osteosarcoma Treatment

Angew Chem Int Ed Engl. 2021 May 10;60(20):11252-11256. doi: 10.1002/anie.202101938. Epub 2021 Apr 8.

Abstract

Supramolecular nanodrug assembly driven by supramolecular chemistry is becoming a powerful strategy for medication. The potential of engineered proteins as building blocks for nanoformulations is rarely investigated. Here, we developed a new generation of recombinant protein-based nanodrug carriers, which is very efficient for loading and delivering the hydrophobic prodrug aldoxorubicin. Significantly enhanced anti-tumor effects in osteosarcoma (OS) models were observed. The half-life of the nanodrug reached almost two days and the corresponding bioavailability increased by 17-fold. This is significantly superior to other drug counterparts, empowering long-acting OS treatment scenarios. Importantly, off-target side effects of the prodrug, including cardiotoxicity and lung-metastasis, were greatly mitigated with our medication. Thus, our assembly strategy enables the customized design of advanced nanodelivery systems employing broader biomaterial building blocks for cancer therapy.

Keywords: engineered proteins; nanodrugs; nanomaterials; osteosarcoma; supramolecular assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics*
  • Biological Availability
  • Bone Neoplasms / drug therapy*
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics
  • Drug Carriers / chemistry
  • Humans
  • Hydrazones / chemistry
  • Hydrazones / pharmacokinetics*
  • Hydrophobic and Hydrophilic Interactions
  • Macromolecular Substances / chemistry
  • Mice
  • Mice, Nude
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Neoplasms, Experimental / drug therapy
  • Osteosarcoma / drug therapy*
  • Particle Size
  • Prodrugs / chemistry
  • Prodrugs / pharmacokinetics*
  • Recombinant Proteins / chemistry

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Hydrazones
  • Macromolecular Substances
  • Prodrugs
  • Recombinant Proteins
  • Doxorubicin
  • DOXO-EMCH