Tumor hypoxia is a common feature of the tumor microenvironment and has been regarded as one of the key factors in driving the emergence of drug resistance in solid tumors. To surmount the hypoxia-associated drug resistance, we fabricated the novel multifunctional liposomal complexes (ACLEP) that could co-deliver oxygen and molecular targeted drug to overcome the hypoxia-induced drug resistance in lung cancer. The ACLEP were fabricated with liposomes anchored with anti-EGFR aptamer-conjugated chitosan to co-administrate erlotinib and PFOB to EGFR-overexpressing non-small-cell lung cancer. Our results showed that the ACLEP possessed desired physicochemistry, good biostability and controlled drug release. The entrapped PFOB in nanoparticle facilitated the uptake of ACLEP in either normoxia or hypoxic condition. Comparing to those nanoparticles loading erlotinib alone, our innovative oxygen/therapeutic co-delivery system showed a promising outcome in fighting against hypoxia-evoked erotinib resistance both in vitro and in vivo. Hence, this work presents a potent drug delivery platform to overcome hypoxia-induced chemotherapy resistance.

中文翻译：

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适体修饰的脂质体复合物共同输送氧和厄洛替尼以逆转低氧诱导的肺癌耐药性

肿瘤缺氧是肿瘤微环境的普遍特征，并被认为是驱动实体瘤中耐药性出现的关键因素之一。为了克服与低氧相关的药物耐药性，我们制造了新型多功能脂质体复合物（ACLEP），可以共同输送氧气和分子靶向药物来克服低氧诱导的肺癌耐药性。ACLEP由脂质体和抗脂质体锚定而成-EGFR适体偶联的壳聚糖可将erlotinib和PFOB共同用于EGFR过表达的非小细胞肺癌。我们的结果表明，ACLEP具有所需的物理化学，良好的生物稳定性和受控的药物释放。包埋在纳米颗粒中的PFOB促进了在常氧或缺氧条件下ACLEP的吸收。与仅载有厄洛替尼的纳米颗粒相比，我们创新的氧气/治疗性共输送系统在对抗体内和体内缺氧引起的埃罗替尼耐药性方面均显示出令人鼓舞的结果。因此，这项工作提出了一个有效的药物输送平台，以克服缺氧诱导的化疗耐药性。