Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350108, China; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350108, China.
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350108, China; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350108, China.
Biomaterials. 2017 Nov;145:56-71. doi: 10.1016/j.biomaterials.2017.08.030. Epub 2017 Aug 18.
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.
肿瘤缺氧是肿瘤微环境的一个常见特征，被认为是导致实体瘤药物耐药性出现的关键因素之一。为了克服与缺氧相关的药物耐药性，我们设计了新型多功能脂质体复合物（ACLEP），能够同时递送氧气和分子靶向药物，以克服肺癌中的缺氧诱导的药物耐药性。ACLEP 是通过带有抗 EGFR 适体偶联壳聚糖的脂质体构建的，以共同给予厄洛替尼和 PFOB 给 EGFR 过表达的非小细胞肺癌。我们的结果表明，ACLEP 具有理想的物理化学性质、良好的生物稳定性和控制药物释放。纳米颗粒中包封的 PFOB 促进了 ACLEP 在常氧或缺氧条件下的摄取。与单独负载厄洛替尼的纳米颗粒相比，我们的创新氧气/治疗联合递送系统在体外和体内均显示出对抗缺氧诱导的厄洛替尼耐药性的有希望的结果。因此，这项工作提出了一种有效的药物递送平台，以克服缺氧诱导的化疗耐药性。
