基于近红外量子点的高效骨靶向纳米药物递送系统用于多发性骨髓瘤的治疗研究

Multiple myeloma is a plasma cancer cell with a strong tropism for bone and bone marrow that has high mortality and disability rates. How to achieve effectively bone marrow-targeted drug delivery is one of the core issues for the treatment of multiple myeloma. Nanoparticle-based targeted drug delivery systems, which are expected to depress the toxic side effects and simultaneously enhance the therapeutic efficiency, have drawn more and more attention. Recent studies indicate that some nanoparticles could cross the blood-bone marrow barrier (BMB) by specific surface functionalization strategies. However, it remains a great challenge to realize precise treatment of tumors in bone marrow. Here we propose a simultaneous bone-targeted and tumor microenvironment-response strategy and will built a near-infrared quantum dot-based nanodrug delivery system. With the help of novel near-infrared II fluorescence imaging technology built by us, surface chemistry-dependent in vivo behaviors of nanodrug delivery systems can be investigated systematically, which can optimize the performance of nanosystems to achieve precise treatment for multiple myeloma. The research results will provide a general strategy for bone-targeted drug delivery, which will lay the foundation for the precise treatment of bone tumors and other bone-associated diseases.

多发性骨髓瘤是一种具有骨归巢特性的浆细胞恶性肿瘤，具有极高的死亡率和致残性。如何实现高效的药物骨髓递送是目前多发性骨髓瘤临床治疗面临的一个焦点问题。靶向纳米药物递送系统因具有高效、稳定的药物输送能力，可降低治疗的系统毒副作用，在肿瘤治疗方面受到广泛的关注。近年来人们基于纳米表面功能化策略初步实现了纳米粒子跨越血-骨髓屏障，但如何实现精准的骨内肿瘤治疗仍面临很大技术挑战。本项目借助我们自主搭建的近红外二区荧光成像技术平台，通过对纳米表面功能化模式的系统考察，根据肿瘤微环境的特点，构建具有高效跨越血-骨髓屏障和肿瘤微环境响应的靶向纳米药物递送系统，实现对多发性骨髓瘤的精准治疗。本项目的研究成果将有助于建立一种通用的纳米药物骨靶向递送策略，为骨肿瘤及其它骨相关疾病的精准治疗奠定技术基础。

由于骨组织的特殊结构及其存在的生理屏障（血-髓屏障），针对骨髓微小残留病灶的高灵敏检测及高效的药物骨髓递送是临床面临的一大挑战。基于近红外II区荧光成像的高组织穿透、高时空分辨及高灵敏度优势，本课题通过设计和制备新型近红外II区荧光量子、肿瘤微环境响应单元结合功能化组装策略，构筑智能型纳米药物递送系统，联合近红外II区活体及显微成像系统，实现对活体肿瘤实时、原位“可视化”的早期诊断和治疗，提高了对骨内等相关肿瘤疾病的发生、发展和治疗机制的认识和理解。