State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
J Control Release. 2023 May;357:40-51. doi: 10.1016/j.jconrel.2023.03.035. Epub 2023 Mar 28.
Cancer immunotherapy is an emerging cancer therapeutic method by activating the patient's immune system but suffers from low immunogenicity at tumor sites. Fever-like heat is known to modulate an immune-friendly tumor microenvironment. Here, temperature-responsive iron oxide nanoassemblies (IONAs) are developed by crosslinking iron oxide nanoparticles (IONPs) and loaded with JQ1 (JQ1/IONAs), an immuno-modulating agent known to down-regulate PD-L1. In the presence of an alternating magnetic field (AMF), the IONAs demonstrate a much more effective magnetic thermal effect than IONPs and are responsively disassembled to prevent overheating. Compared with IONPs + AMF (∼ 41 °C) and unresponsive nanoassemblies (uIONAs) + AMF (∼ 50 °C), the IONAs + AMF with a temperature heated around 45 °C show a much better immune response and anti-tumor effect. Further combining the mild thermal therapy with controlled release of JQ1, the JQ1/IONAs + AMF completely eradicate the primary tumors and trigger a strong immune effect to inhibit the distant tumor growth as well as prevent tumor recurrence and metastasis. Our JQ1/IONAs not only provide a magnetic thermal agent with effective heating and temperature self-regulation ability but also serve as a heat-triggered JQ1 carrier to spontaneously combine mild magnetic thermal therapy with immune checkpoint blockade therapy.
癌症免疫疗法是一种新兴的癌症治疗方法，通过激活患者的免疫系统，但在肿瘤部位的免疫原性较低。众所周知，发热样热可以调节免疫友好型肿瘤微环境。在这里，通过交联氧化铁纳米颗粒 (IONPs) 并负载 JQ1（一种已知下调 PD-L1 的免疫调节剂）来开发温度响应型氧化铁纳米组装体 (IONAs)。在交变磁场 (AMF) 的存在下，IONAs 表现出比 IONPs 更有效的磁热效应，并且可以响应性地解组装以防止过热。与 IONPs + AMF（约 41°C）和无响应纳米组装体（uIONAs）+ AMF（约 50°C）相比，温度加热到约 45°C 的 IONAs + AMF 显示出更好的免疫反应和抗肿瘤效果。进一步将温和的热疗与 JQ1 的控制释放相结合，JQ1/IONAs + AMF 可完全根除原发性肿瘤，并引发强烈的免疫效应，抑制远处肿瘤的生长，防止肿瘤复发和转移。我们的 JQ1/IONAs 不仅提供了一种具有有效加热和温度自调节能力的磁热剂，而且还作为热触发的 JQ1 载体，将温和的磁热疗法与免疫检查点阻断疗法自发结合。
