基于天然黑色素纳米颗粒在双模态分子成像引导下癌症治疗的研究

With the approval of nano-materials as drug carriers used in clinic, the treatment of cancer has been injected new prospect. However, due to the problems like toxicity, degradability, biocompatibility and synthesis, the clinical application of nano-materials is limited. Selecting human endogenous melanin as nano-carrier could solve these problems effectively. Our team has overcome these difficulties such as poor solubility and large particle size, offering a non-toxic, water-soluble, micro-sized and multifunctional melanin nano-particle (MNP). The project intends to use MNP’s capacity for absorbing drugs to load anti-cancer drug Sorafenib and combine the nano-carrier’s EPR effect targeting transport of drugs to tumor tissue. The anti-cancer effect can be enhanced greatly. To use the capacity for easily binding metal irons to load Gd3+ and combine photoacoustic character about itself, achieving MR and PAI double modality imaging. At the same time, we can construct a molecular function and anatomy to guide the cancer treatment under the image. The novel multifunctional nano-probe integrates drug targeting transport, drug therapy, double modal molecular imaging and outcome monitoring in a whole. It’s also expected to be used in integrated cancer treatment. It has practical significance in prompting nano-materials transformed into cancer diagnosis and treatment.

随着纳米材料作为药物的载体被批准应用于临床，给癌症的治疗注入了新的希望。然而，由于纳米材料的毒性、降解性、生物相容性和合成工艺等问题，使其临床应用受到了限制。选择人体内源性天然物质黑色素作为纳米载体，有望解决这些难题。项目组前期攻克了黑色素纳米颗粒（MNP）水溶性差、粒径大的难关，提供了一种无毒、水溶、小尺寸、多功能的纳米颗粒。本项目拟利用MNP可吸附药物的特性加载抗癌靶向药索拉菲尼，并结合自身的EPR效应靶向输送药物到肿瘤组织，增强抗癌效果；利用MNP易螯合金属离子的特性加载Gd3+，并结合自身的光声特性，实现MRI和PAI双模态分子成像，将分子功能和解剖结构的图像信息有机结合，为图像引导下癌症治疗提供依据。这种新颖的多功能纳米探针整合药物靶向运输、药物治疗、双模态分子成像和疗效监测等功能于一体，有望成为一种新型的多功能纳米制剂用于癌症的诊疗，推动纳米材料向临床转化具有现实意义。

纳米技术的快速发展为肿瘤诊疗提供了新的机遇，借助多种分子成像手段对肿瘤部位进行实时监测，对于提高肿瘤诊断的准确性和改善预后具有重要意义。然而，现有纳米材料的潜在毒性、降解性和生物相容性等问题限制了其进一步的临床应用。本项目选用人体内源性天然物质黑色素作为纳米载体，攻克了前期黑色素纳米颗粒（MNP）水溶性差、粒径大等难关，合成了一种无毒、水溶性好、尺寸小的黑色素纳米颗粒。利用该纳米颗粒可负载药物的特性加载抗癌靶向药索拉菲尼，增强了药物的肿瘤靶向治疗效果；利用MNP易螯合金属离子的特性加载Gd3+，并结合自身的光声成像特性，实现了MRI和PAI双模态分子成像，有助于进一步对肿瘤部位进行图像引导下的治疗和疗效监测。该多功能黑色素纳米颗粒将药物靶向运输和分子成像功能整合于一体，为实现癌症的诊疗一体化带来了新的机遇，对于推动纳米医药向临床的转化具有现实意义。