恶性黑色素瘤（CMM）是最常见的皮肤恶性肿瘤，其突变率和恶性程度高、转移早、预后差。现有治疗药物因毒副作用大且易产生耐药，难以实现对其有效治疗。已有研究表明超顺磁性氧化铁纳米粒（SPION）等新型药物递送系统是实现其有效治疗的重要手段。我们前期研究已发现SPION在磁场调控下可有效穿透各类致密生物屏障，显著提高治疗药物表柔比星（EPI）的靶向分布；其表面修饰后可高效嫁接EPI、肌肽等药物，实现药物的可调式释放，且局部滞留的高浓度SPION具有协同诱导细胞发生氧化应激作用。本项目拟在此基础上，开展EPI-SPION递药系统优化研究，通过磁响应性经皮递送并利用CMM组织低pH值微环境精准触发药物释放，避免首过效应及其他毒副作用，实现对CMM高效治疗。本研究将探索CMM病变部位精准靶向的效果与机制、载体材料的协同作用，为拓展新型递药系统和CMM治疗提供创造性研究思路。

Cutaneous malignant melanoma (CMM) is the most common skin malignant tumor with high mutation rate and malignant degree, early metastasis and poor prognosis. Efficacy of drugs utilized in present clinical treatments is always limited by the their side effects and drug resistance. Novel drug targeting delivery system is an effective means to treat CMM safely and efficiently. The superparamagnetic iron-oxide nanoparticles (SPION) have been enthusiastically investigated in recent decades as a ultrasmall drug vector. Our previous studies have found that SPION can effectively penetrate various biological barriers under the action of external force, significantly improve the antitumor drug Epirubicin (EPI) distribution. After surface functional modification, EPI and other therapeutic molecular such as carnosine can be efficiently grafted onto SPION and achieve tailored release of therapeutic agents. The high concentration of SPION retension has been proved to induce the oxidative stress and immunologic inflamation porcess. Based on our previous breakthrough findings, we are going to optimize the EPI-SPION drug delivery system. We plan to use the magnetic transdermal delivery technique and conbine the pH-sensitive durg release mechanism, avoiding the first-pass effect and other side actions, so as to achieve effective treatment for CMM pharmacotherapy. Our research will explore the effect and mechanism of precise targeting, synergy of carrier materials, to develop a brand-new drug delivery system and provide creative thinking for CMM treatment.