Tumor hypoxia-associated drug resistance presents a major challenge for cancer chemotherapy. However, sustained delivery systems with a high loading capability of hypoxia-inducible factor-1 (HIF-1) inhibitors are still limited. Here, we developed an ultrastable iodinated oil-based Pickering emulsion (PE) to achieve locally sustained codelivery of a HIF-1 inhibitor of acriflavine and an anticancer drug of doxorubicin for tumor synergistic chemotherapy. The PE exhibited facile injectability for intratumoral administration, great radiopacity for in vivo examination, excellent physical stability (>1 mo), and long-term sustained release capability of both hydrophilic drugs (i.e., acriflavine and doxorubicin). We found that the codelivery of acriflavine and doxorubicin from the PE promoted the local accumulation and retention of both drugs using an acellular liver organ model and demonstrated significant inhibition of tumor growth in a 4T1 tumor-bearing mouse model, improving the chemotherapeutic efficacy through the synergistic effects of direct cytotoxicity with the functional suppression of HIF-1 pathways of tumor cells. Such an iodinated oil-based PE provides a great injectable sustained delivery platform of hydrophilic drugs for locoregional chemotherapy.

中文翻译：

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超稳定碘化油基 Pickering 乳液可实现缺氧诱导因子 1 抑制剂和抗癌药物的局部持续共递送，用于肿瘤联合化疗

肿瘤缺氧相关的耐药性对癌症化疗提出了重大挑战。然而，具有高负载能力的缺氧诱导因子-1 (HIF-1) 抑制剂的持续递送系统仍然有限。在这里，我们开发了一种超稳定的碘化油基皮克林乳液（PE），以实现吖啶黄HIF-1抑制剂和阿霉素抗癌药物的局部持续共递送，用于肿瘤协同化疗。 PE表现出易于瘤内给药的可注射性、用于体内检查的良好的射线不透性、优异的物理稳定性（>1个月）以及两种亲水性药物（即吖啶黄和阿霉素）的长期缓释能力。我们发现，在无细胞肝器官模型中，PE 中的吖啶黄和阿霉素的共同递送促进了两种药物的局部积累和保留，并在 4T1 荷瘤小鼠模型中显示出对肿瘤生长的显着抑制，通过协同作用提高了化疗效果。直接细胞毒性作用与肿瘤细胞 HIF-1 通路的功能性抑制。这种基于碘化油的PE为局部化疗提供了良好的亲水性药物注射持续递送平台。