Ultrastable Iodinated Oil-Based Pickering Emulsion Enables Locoregional Sustained Codelivery of Hypoxia Inducible Factor-1 Inhibitor and Anticancer Drugs for Tumor Combination Chemotherapy

作者：Zhihua Li, Xiaoya Liu, Jingyu Xiao, Hang Jiang, Le Ma, Yucheng Luo, Meijuan Wang, Yuwei Zhu, Hongliang Jiang, Hanyang Yao, To Ngai, Qiongyu Guo · 发表于：ACS Biomaterials Science & Engineering · 年份：2024 · DOI：10.1021/acsbiomaterials.3c01887 · 被引用次数：7 · 研究领域：Micro and Nano Robotics、Pickering emulsions and particle stabilization、Nanoparticle-Based Drug Delivery

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.