pH-responsive mesoporous ZSM-5 zeolites/chitosan core-shell nanodisks loaded with doxorubicin against osteosarcoma

Mater Sci Eng C Mater Biol Appl. 2018 Apr 1:85:142-153. doi: 10.1016/j.msec.2017.12.024. Epub 2017 Dec 21.

Abstract

Oral or intravenous chemotherapy is an important strategy to treat metastatic cancer, but it may cause systemic toxicity for healthy tissue. Herein, we for the first time fabricated mesoporous ZSM-5 zeolites/chitosan core-shell nanodisks loaded with doxorubicin (ZSM-5/CS/DOX) as drug delivery systems against osteosarcoma. The mesoporous ZSM-5 zeolites exhibited disk-like shapes with thicknesses of 100nm and diameters of 300nm, and the mesopores with pore sizes of 3.75nm were originated from desilication treatment. The pH-responsive ZSM-5/CS/DOX nanodisks possessed a great drug loading efficiency of 97.7%, and their controlled release trends of DOX were fitted well with the Korsmeyer-Peppas model. The DOX could be efficiently released the ZSM-5/CS/DOX nanodisks after cellular endocytosis and induced cancer cells apoptosis. Moreover, the pH-responsive drug carriers led to efficient tumor inhibition with low side effects, especially cardiac toxicity, as confirmed by pharmacokinetic study, serological examination and H&E staining assays. Therefore, the ZSM-5/CS/DOX nanodisks are a promising pH-responsive drug carrier for targeted cancer therapy.

Keywords: Chitosan; Cytotoxicity; Osteosarcoma; ZSM-5 zeolite; pH-responsive.

MeSH terms

  • Adult
  • Animals
  • Biomarkers / metabolism
  • Cell Death
  • Cell Line, Tumor
  • Chitosan / chemistry*
  • Doxorubicin / blood
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use*
  • Humans
  • Hydrogen-Ion Concentration
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mesenchymal Stem Cells / cytology
  • Models, Biological
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Nitrogen / chemistry
  • Osteosarcoma / drug therapy*
  • Porosity
  • Rats, Sprague-Dawley
  • Temperature
  • Tissue Distribution
  • X-Ray Diffraction
  • Zeolites / chemistry*

Substances

  • Biomarkers
  • ZSM-5 zeolite
  • Zeolites
  • Malondialdehyde
  • Doxorubicin
  • Chitosan
  • L-Lactate Dehydrogenase
  • Nitrogen