纳米药物的肿瘤靶向性递送对于提高其体内功效、降低毒副作用至关重要。三阴乳腺癌表面缺乏特异性受体，严重限制了靶向纳米药物的应用。本项目拟研究一种新型的肿瘤靶向技术—“固定点击反应介导的组织主动靶向（ATTACK）”，利用糖代谢人为地在肿瘤细胞膜表面引入叠氮基团实现肿瘤特异性标记，并经生物正交“点击”反应实现纳米药物肿瘤靶向。针对ATTACK技术介导的纳米药物肿瘤靶向中的几个关键问题，拟开展以下研究。（1）通过调控唾液酸类似物的亲疏水性和刺激敏感性优化其肿瘤细胞标记效率和选择性；（2）研究ATTACK技术介导纳米载体肿瘤靶向的有效性，并通过调控纳米药物粒径和表面DBCO基团密度优化靶向效率；（3）设计PEG脱除系统并结合穿膜肽，解决纳米载体经ATTACK途径入胞后较难逃逸内涵体/溶酶体的问题，提高其体内外功效。本研究对于纳米药物肿瘤主动靶向递送、三阴乳腺癌的纳米靶向治疗具有重要意义。

Targeted delivery of nanomedicine toward tumor tissues/cells plays a critical role in enhancing their therapeutic efficacy and reducing side effect. Triple negative breast cancer (TNBC) lacks specific receptors, which greatly hurdles the utility of cancer-targeted nanomedicine. In this proposed study, we aim to develop a novel cancer active-targeting strategy, "active tissue targeting via anchored click chemistry (ATTACK)", to realize the in vivo cancer targeting via sugar metabolism and bioorthogonal click reaction. Particularly, we first plan to manipulate the hydrophilicity/hydrophobicity of the sugar molecules to maximize its labeling efficiency in cancer cells. Second, we will testify the capability of ATTACK strategy in mediating cancer targeted delivery of nanocarriers. Thirdly, we will further design PEG sheddable and CPP-exposable nanosystems to promote the endosomal/lysosomal escape of nanocarriers post internalization via the ATTACK process. This study will therefore provide profound significance for the targeted treatment of TNBC by using nanomedicine.