GOx-assisted synthesis of pillar[5]arene based supramolecular polymeric nanoparticles for targeted/synergistic chemo-chemodynamic cancer therapy

J Nanobiotechnology. 2022 Jan 11;20(1):33. doi: 10.1186/s12951-021-01237-0.

Abstract

Background: Cancer is the most serious world's health problems on the global level and various strategies have been developed for cancer therapy. Pillar[5]arene-based supramolecular therapeutic nano-platform (SP/GOx NPs) was constructed successfully via orthogonal dynamic covalent bonds and intermolecular H-bonds with the assistance of glucose oxidase (GOx) and exhibited efficient targeted/synergistic chemo-chemodynamic cancer therapy.

Methods: The morphology of SP/GOx NPs was characterized by DLS, TEM, SEM and EDS mapping. The cancer therapy efficinecy was investigated both in vivo and in vitro.

Results: SP/GOx NPs can load drug molecules (Dox) and modify target molecule (FA-Py) on its surface conveniently. When the resultant FA-Py/SP/GOx/Dox NPs enters blood circulation, FA-Py will target it to cancer cells efficiently, where GOx can catalyst the overexpressed glucose to generate H2O2. Subsequently, the generated H2O2 in cancer cells catalyzed by ferrocene unit to form •OH, which can kill cancer cells. Furthermore, the loaded Dox molecules released under acid microenvironment, which can further achieve chemo-therapy.

Conclusion: All the experiments showed that the excellent antitumor performance of FA-Py/SP/GOx/Dox NPs, which provided an new method for pillar[5]arene-based supramolecular polymer for biomedical applications.

Keywords: Host-guest interactions; Pillar[5]arene; Supramolecular polymers; Synergistic therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / metabolism
  • Antineoplastic Agents* / pharmacology
  • Calixarenes* / chemistry
  • Calixarenes* / metabolism
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Synergism
  • Glucose Oxidase* / chemistry
  • Glucose Oxidase* / metabolism
  • Hydrogen Peroxide
  • Mice
  • Nanoparticles* / chemistry
  • Nanoparticles* / metabolism
  • Polymers / chemistry
  • Polymers / metabolism
  • Quaternary Ammonium Compounds* / chemistry
  • Quaternary Ammonium Compounds* / metabolism

Substances

  • Antineoplastic Agents
  • Polymers
  • Quaternary Ammonium Compounds
  • pillar(5)arene
  • Calixarenes
  • Doxorubicin
  • Hydrogen Peroxide
  • Glucose Oxidase