缺氧(环境)
肿瘤缺氧
光热治疗
癌症研究
化学
体内
生物物理学
材料科学
纳米技术
医学
生物
氧气
放射治疗
内科学
生物技术
有机化学
作者
Xudong Li,Yuran Wang,Hui Chen,Yilin Zheng,Haijun Chen,Xiumei Li,Yu Gao
标识
DOI:10.1016/j.apmt.2022.101660
摘要
Tumor hypoxic microenvironment contributes to AZD9291 (osimertinib) resistance in non-small cell lung cancer (NSCLC). Developing hypoxia-triggered theranostic formulation for simultaneous hypoxia tumor imaging and oxygen-independent photothermal therapy (PTT) will be an effective strategy to overcome AZD9291 resistance under hypoxic conditions. Herein, we designed and synthesized a boron-dipyrromethene (BODIPY) dye-modified chitosan (CsB) linked through a hypoxia-responsive azobenzene group and fabricated a nanoplatform CsBANs self-assembled by CsB and AZD9291 to achieve hypoxia-responsive imaging and synergistic PTT/targeted molecular therapy. CsBANs exhibited excellent cellular uptake efficiency and hypoxia imaging capacity either in two-dimensional NSCLC cell cultures under hypoxia or in multicellular tumor spheroids. The in vitro and in vivo results showed that the photothermal effects of BODIPY and AZD9291 could induce satisfactory anticancer effects in NSCLC cell lines and in xenograft mouse model. Hence, this work presents a promising hypoxia-activated nanotheranostic platform to deal with hypoxia-induced AZD9291 resistance and for other hypoxia-related diseases.
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