An intelligent hypoxia-relieving chitosan-based nanoplatform for enhanced targeted chemo-sonodynamic combination therapy on lung cancer

被引：30

作者：

Zhang, Peixia ^{[1
]}

Zhang, Lu ^{[1
]}

Wang, Jun ^{[1
]}

Zhu, Lisheng ^{[1
]}

Li, Ziying ^{[1
]}

Chen, Haijun ^{[2
]}

Gao, Yu ^{[1
]}

机构：

[1] Fuzhou Univ, Coll Chem, Canc Metastasis Alert & Prevent Ctr, Fujian Prov Key Lab Canc Metastasis Chemoprevent, Fuzhou 350108, Fujian, Peoples R China

[2] Fuzhou Univ, Fujian Prov Key Lab Canc Metastasis Chemoprevent, Fuzhou 350108, Fujian, Peoples R China

来源：

CARBOHYDRATE POLYMERS | 2021年 / 274卷

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

Non-small cell lung cancer; Chitosan; Sonodynamic therapy; Erlotinib; Perfluoroctylbromide; Hypoxia; PHOTODYNAMIC THERAPY; DRUG-DELIVERY; CO-DELIVERY; RESISTANCE; METASTASIS; ANTICANCER; ERLOTINIB; OXYGEN;

D O I：

10.1016/j.carbpol.2021.118655

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

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.

引用

页数：13

共 54 条

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