Evaluation on EPR effect and active control of EPR effect for achieving efficient tumor accumulation of nanocarrier delivery system

利用纳米载体进行化疗，可以使化疗药物在肿瘤组织中高蓄积，但由于所谓的“增强渗透性和滞留性（EPR）效应”，在健康器官中蓄积有限，从而改善实体肿瘤的临床治疗。我们发现，低剂量节律化疗对生长中的肿瘤血管内皮细胞和肿瘤细胞造成损伤，由于实体瘤血管正常化和瘤内空间扩大，纳米载体在肿瘤中的积累增加。该策略可能是纳米载体抗癌药物治疗血管密度和通透性较低的顽固性肿瘤的突破性进展。

Chemotherapy delivered in nanocarriers has been developed to improve the clinical treatment of solid tumors by achieving high accumulation of chemotherapeutic agents in tumor tissues but limited accumulation in healthy organs via due to the so-called" enhanced permeability and retention(EPR) effect". We showed that low dose metronomic chemotherapy given the damage in endothelial cells of growing tumor vasculature and tumor cells, increased tumor accumulation of nanocarriers as a result of vascular normalization and enlargement of intratumoral space in solid tumors. This strategy may be breakthrough in anti-cancer chemotherapy with nanocarrier-based anticancer drugs against intractable tumors which have lower vascular density and permeability.