葡聚糖微胶囊在多种原位恶性肿瘤模型中的多模示踪及药物传输

Glucan particles, derived from the common baker’s yeast, are hollow microspheres, and the shells with thickness of 200-300 nm are composed of beta-1,3-glucan. The high biocompatibility and porous shell and large hollow space make them can served as micron-sized carriers to deliver and release kinds of agents in body. In our previous studies, we have firstly discovered that GPs microcapsules can effectively migrate into the tumor microenvironment and break through blood-brain barrier through oral administration, or by intraperitoneal or intravenous injection in various tumor-bearing models. However, the optimized dosage regimen needed by the best curative effect call for comprehensive evaluation on in vivo pharmacokinetics of glucan capsules. To tracking the path of glucan particles in vivo, we will design multi-modal imaging coupling three complementary imaging modelities: fluorescence, photoacoustic, and magnetic resonance imaging. Tumor heterogeneity may be a major reason for the poor treatment efficacy and the development of chemoresistance. Therefore, targeted multi-drug therapy is a valuable option for addressing the multiple mechanisms that may be responsible for reduced efficacy of current therapies after entrapped these drugs into the GPs carriers. The potential strategies may enhance the drug-carrier performance in malignant tumors including pancreatic carcinoma or glioma. We can use these methods and exactly observe the pharmacokinetics, biodistribution, and long-term fate of therapeutic or imaging molecules for promising anti-cancer ability in tumor microenvironment. The multi-modal, multi-scale imaging and therapy technologies have emerged to improve our insight into these processes. Theranostic imaging agents have provided real-time and quantitative readouts of drug distribution and therapeutic response, which can provide the ideal application to further catalyze clinical translation.

葡聚糖微胶囊（glucan particles, GPs）,源于面包酵母，由beta-1,3-葡聚糖三螺旋纳米纤维缠绕而成,具有天然的中空多孔结构。我们首次发现，GPs能穿过小鼠血脑屏障,且能靶向到肿瘤微环境。但其体内动力学和最优给药方案仍缺少认知，而阻碍了其应用开发。本项目拟基于已建立的受限空间内原位制备/化学修饰/物理装载技术实现多种功能纳米材料在葡聚糖微胶囊中的共装载，获得兼具荧光、光声、磁性、CT等多信号的GPs微胶囊；继而用多种原位恶性肿瘤模型如胰腺癌、脑胶质瘤等详细追踪葡聚糖微胶囊的体内路径，并借以指导葡聚糖为载体药物的给药方案；并进一步制备单组分/多协同组分共担载的葡聚糖微胶囊，评价其在优化给药方案下的药物靶向和抑瘤效果。通过四年的项目实施，有望获得较为系统的临床前期数据，为实现恶性肿瘤微纳米医药的研发提供理论依据。项目后期将与制药企业接洽，以推动创新药物的临床转化研究。

葡聚糖微胶囊（glucan particles, GPs）,源于面包酵母，由beta-1,3-葡聚糖三螺旋纳米纤维缠绕而成,具有天然的中空多孔结构。我们研究发现，GPs能穿过小鼠血脑屏障,且能靶向到肿瘤微环境，但是其体内动力学和最优给药方案仍有待研究，而阻碍了其应用开发。本课题拟基于已建立的受限空间内原位制备/化学修饰/物理装载技术实现多种功能纳米材料在葡聚糖微胶囊中的共装载，获得兼具荧光、光声、磁性、CT等多信号的GPs微胶囊，进而研究：1.用多种原位恶性肿瘤模型如胰腺癌、脑胶质瘤等详细追踪葡聚糖微胶囊的体内路径，并借以指导葡聚糖为载体药物的给药方案；2.制备单组分/多协同组分共担载的葡聚糖微胶囊，评价其在优化给药方案下的药物靶向和抑瘤效果。从而获得较为系统的临床前期数据，为实现恶性肿瘤微纳米医药的研发提供理论依据，并计划与制药企业接洽，以推动创新药物的临床转化研究。