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Updated: Oct 15, 2025

Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
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.
Abstract:
The clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs)-based targeted molecular therapies (TMT) is inevitably hampered by the development of acquired drug resistance in non-small cell lung cancer (NSCLC) treatment. Sonodymanic therapy (SDT) is a promising new cancer treatment approach, but its effects are restricted by tumor hypoxia. Herein, a nanoplatform fabricated by erlotinib-modified chitosan loading sonosensitizer hematoporphyrin (HP) and oxygen-storing agent perfluorooctyl bromide (PFOB), namely CEPH, was developed to deliver HP to erlotinib-sensitive cells. CEPH with ultrasound could alleviate hypoxia inside the three-dimensional multicellular tumor spheroids, suppress NSCLC cell growth under normoxic or hypoxic condition, and enhance TMT/SDT synergistic effects through elevated production of reactive oxygen species, decrease of mitochondrial membrane potential, and down-regulation of the expression of the proteins EGFR, p-EGFR, and HIF-1α. Hence, CEPH could be a potential nanoplatform to improve the efficacy of oxygen-dependent SDT and overcome hypoxia-induced TMT resistance for enhanced synergistic TMT/SDT.
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.
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