An intelligent hypoxia-relieving chitosan-based nanoplatform for enhanced targeted chemo-sonodynamic combination

Peixia Zhang1, Lu Zhang1, Jun Wang1

  • 1Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China.

Carbohydrate Polymers
|October 27, 2021
PubMed

Insights

This study introduces CEPH, a novel nanoplatform that combines targeted therapy and sonodynamic therapy to overcome drug resistance in non-small cell lung cancer (NSCLC). CEPH effectively combats tumor hypoxia, enhancing treatment efficacy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) limits non-small cell lung cancer (NSCLC) treatment efficacy.
  • Tumor hypoxia restricts the effectiveness of sonodynamic therapy (SDT), a promising cancer treatment.

Purpose of the Study:

  • To develop a nanoplatform (CEPH) for enhanced synergistic targeted molecular therapy (TMT) and SDT in NSCLC.
  • To overcome hypoxia-induced TMT resistance and improve SDT efficacy.

Main Methods:

  • Fabrication of erlotinib-modified chitosan loaded with hematoporphyrin (HP) and perfluorooctyl bromide (PFOB) as CEPH.
  • Evaluation of CEPH's ability to alleviate tumor hypoxia in 3D multicellular tumor spheroids.
  • Assessment of CEPH's impact on NSCLC cell growth, reactive oxygen species production, mitochondrial membrane potential, and protein expression (EGFR, p-EGFR, HIF-1α) under normoxic and hypoxic conditions.

Main Results:

  • CEPH effectively delivered HP to erlotinib-sensitive cells.
  • Ultrasound-activated CEPH alleviated tumor hypoxia and suppressed NSCLC cell growth.
  • Enhanced synergistic TMT/SDT effects were observed, including increased reactive oxygen species, decreased mitochondrial membrane potential, and down-regulation of EGFR, p-EGFR, and HIF-1α.

Conclusions:

  • CEPH is a potential nanoplatform for improving oxygen-dependent SDT.
  • CEPH can overcome hypoxia-induced TMT resistance in NSCLC.
  • CEPH facilitates enhanced synergistic TMT/SDT for improved NSCLC treatment.