仿巨噬细胞纳米乳清除炎症因子促进多发性骨髓瘤的化疗研究

复发难治性多发性骨髓瘤是多发性骨髓瘤治疗领域的难点问题，设计新的治疗策略提高其疗效具有重要的研究意义和临床价值。骨髓微环境对骨髓瘤细胞的支持保护并促进其耐药形成是导致多发性骨髓瘤复发难治的重要支持因素。作为骨髓微环境中的重要成分，巨噬细胞炎性蛋白1α（MIP-1α）和破骨细胞与骨髓瘤细胞三者之间相互支持相互促进，共同推动多发性骨髓瘤的复发难治。据此，本项目采用仿巨噬细胞纳米乳包载模型药物硼替佐米构建一种新型的仿生纳米递药系统。该仿生纳米递药系统具备长循环及药物缓释的特性，一方面，通过吸附清除MIP-1α而抑制破骨细胞分化和骨髓瘤细胞的增殖迁移播散，同时增加骨髓瘤细胞对硼替佐米的治疗敏感性；另一方面，通过主动靶向效应高效递送硼替佐米，从而提高其化疗效果。该多发性骨髓瘤治疗策略目前国内外未见报道，具有较好的新颖性和研究价值。

Relapsed/refractory multiple myeloma poses a great challenge, and it is of high importance and clinical value to develop new strategy to improve the therapeutic effect for relapsed/refractory multiple myeloma. Bone marrow microenvironment which can support and protect myeloma cells and drive drug resistance of myeloma cells is a crucial contributor to relapsed/refractory multiple myeloma. The key component of bone marrow microenvironment such as macrophage inflammation protein-1α (MIP-1α)，osteoclast and myeloma cells interdependently and mutually affect each other, which jointly promote drug resistance and relapse in MM. Here, we try to design a new biomimetic nano drug delivery system by using macrophage-mimicking nanoemulsions encapsulating bortezomib as the model drug. This drug delivery system is characteristic of long circulation time and slow drug release. On the one hand it could bind and remove MIP-α, which not only help inhibit the formation of osteoclast and the proliferation, migration and spread of myeloma cell, but also increase the drug sensitivity of myeloma cells. On the other hand, it could actively target the tumor site and increase the delivery of bortezomib, and therefore improve the therapeutic effect for multiple myeloma. The therapeutic strategy has never been reported in domestic and abroad and presented high-level research value and innovation significance.