肿瘤血管"正常化"是抗血管生成药物治疗肿瘤应用中具有重要意义的全新作用机制，"节拍式化疗"作为一种新型肿瘤抗血管生成治疗策略是否也具有诱导肿瘤血管"正常化"的作用，尚未见相关研究报道。本项目以靶向肿瘤血管内皮细胞特异性高表达的KDR受体的K237多肽修饰的紫杉醇（PTX）隐形纳米粒（K237-PTX-NP）为给药系统模型，首次开展靶向纳米给药系统"节拍式化疗"诱导肿瘤血管"正常化"的探索性研究，考察各主要肿瘤血管"正常化"特征参数和肿瘤组织微环境参数在"节拍式化疗"中的动力学变化，探讨"节拍式化疗"诱导肿瘤血管"正常化"的作用和分子机制，评价在肿瘤血管"正常化窗口"期间协同细胞毒性化疗增强抗肿瘤作用的效应。本研究将为"节拍式化疗"和肿瘤血管"正常化"的基础和临床研究的发展、以及靶向肿瘤血管纳米给药系统的发展提供新的理论思路和指导作用。

Normalization of tumor vasculature is a newly revealed paramount mechanism of clinical antiangiogenic drugs for cancer therapy. Metronomic chemotherapy is a novel antiangiogenic strategy developed over the past 10 years, but whether or not metronomic chemotherapy has the nature of normalizing tumor vasculature has not been documented yet. In this study, K237-PTX-NP, paclitaxel loaded stealth nanoparticles decorated with K237 peptide that can target KDR receptors highly expressed in the tumor vascular endothelial cells, are chosen as the model for metronomic chemotherapy. For the first time, the potential of utilizing metronomic chemotherapy to normalize tumor vessel will be explored through monitoring the dynamic changes of various characteristic parameters of tumor vessel and microenvironment, dissecting the effect of normalizing tumor vessel and the underlying molecular mechanism, and evaluating the enhanced antitumor efficacy of conventional cytotoxic chemotherapy during the "normalization window". Our investigation will provide new theoretical ideas and guidance in the development of metronomic chemotherapy, tumor vessel normalization, and tumor vessel targeted nanoparticulate drug delivery system.