pH-Sensitive nanoparticles based on amphiphilic imidazole/cholesterol modified hydroxyethyl starch for tumor chemotherapy

Carbohydr Polym. 2022 Feb 1:277:118827. doi: 10.1016/j.carbpol.2021.118827. Epub 2021 Nov 10.

Abstract

pH-Responsive nanoparticles (NPs) have emerged as an effective antitumor drug delivery system, promoting the drugs accumulation in the tumor and selectively releasing drugs in tumoral acidic microenvironment. Herein, we developed a new amphiphilic modified hydroxyethyl starch (HES) based pH-sensitive nanocarrier of antitumor drug delivery. HES was first modified by hydrophilic imidazole and hydrophobic cholesterol to obtain an amphiphilic polymer (IHC). Then IHC can self-assemble to encapsulate doxorubicin (DOX) and form doxorubicin-loaded nanoparticles (DOX/IHC NPs), which displayed good stability for one week storage and acidic sensitive long-term sustained release of DOX. As a result, cancer cell endocytosed DOX/IHC NPs could continuously release doxorubicin into cytoplasm and nucleus to effectively kill cancer cells. Additionally, DOX/IHC NPs could be effectively enriched in the tumor tissue, showing enhanced tumor growth inhibition effect compared to free doxorubicin. Overall, our amphiphilic modified HES-based NPs possess a great potential as drug delivery system for cancer chemotherapy.

Keywords: Amphipathic polymer; Antitumor activity; Drug delivery; Nanocarrier; pH-response.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cholesterol / chemistry*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers / chemistry
  • Drug Liberation
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Hydroxyethyl Starch Derivatives / chemistry*
  • Imidazoles / chemistry*
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Particle Size
  • Surface-Active Agents / chemistry*
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Hydroxyethyl Starch Derivatives
  • Imidazoles
  • Surface-Active Agents
  • imidazole
  • Doxorubicin
  • Cholesterol