用于肝转移瘤早期探测的可激活近红外荧光纳米探针研究

肝转移瘤的早期探测是肿瘤成像领域的难点，近红外荧光成像是转移瘤早期探测领域的一个新方向。本申请拟采用pH 、还原双响应的聚氧乙烯-b-聚氨基酸嵌段聚合物胶束高效包载近红外荧光探针吲哚菁绿（ICG），诱导其在胶束可交联内核中荧光淬灭；通过胶束诱导ICG在微小肝转移瘤病灶的富集、渗透，并进一步利用胶束双重响应的特点，诱导其在肿瘤细胞内响应性解离，释放ICG并激活其近红外光荧光特性，从而增强其在肝转移瘤病灶的荧光信号响应性。通过调控ICG胶束的理化特性，优化纳米探针的生物分布及代谢行为，实现其在肝正常组织的快速消除、在肝转移瘤的长期滞留，从而优化其近红外荧光成像的信噪比，并进一步探索纳米探针对不同尺寸微小肝转移瘤的识别能力。这种可激活的纳米探针不仅可用于微小转移瘤的超灵敏探测，在原位肿瘤早期探测、可视化肿瘤切除手术及肿瘤光热治疗等领域也有重要的理论意义和应用价值。

It is a major challenge to detect early liver metastasis in field of cancer imaging. Near-infrared fluorescent imaging is a new focus in field of the detection of early tumor metastasis.In this application, we develop a pH- and reduction- responsive polymeric micelle nanoprobe for encapsulating indocyanine green (ICG), which can be quenched significantly because of the high concentration of ICG in cross-linked micellar cores. The micelles can induce the accumulation and penetration of ICG in the liver metastasis lesion, and then dissociate responding to low pH and reduction environment in tumor cells, which can further facilitate the release of ICG from the micelles and subsequent activitation of near infrared fluorescence of ICG for enhanced fluorescent imaging signals.The pharmacokinetic behavior and biodistribution of the nanoprobe are optimized for achieving the rapid excretion in normal liver tissue and long retention in liver metastasis, which can significantly improve the signal-to-noise ratio. Finally, the nanoprobe is used to detect the liver metastasis with various size. The activable nanoprobe is not only used for ultrasensitive detection of early metastasis, but also the orthotopic detection, visible excision surgery of tumor and photothermal therapy.