Journal
CARBOHYDRATE POLYMERS
Volume 274, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2021.118655
Keywords
Non-small cell lung cancer; Chitosan; Sonodynamic therapy; Erlotinib; Perfluoroctylbromide; Hypoxia
Categories
Funding
- National Natural Science Foundation of China [81871481, 81571802]
- National Key R&D Program of China [2020YFA0210800]
- Fujian Provincial Youth Top-notch Talent Support program, China
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CEPH nanoplatform has the potential to enhance the efficacy of oxygen dependent SDT and overcome hypoxia-induced TMT resistance for improved synergistic TMT/SDT, by alleviating hypoxia, suppressing NSCLC cell growth, and enhancing the production of reactive oxygen species through ultrasound activation.
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-1 alpha. 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.
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