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

已经开发了在纳米载体中递送的化学疗法，以通过实现化学治疗剂在肿瘤组织中的高积累，但由于所谓的”增强的渗透性和保留（EPR）效应”而在健康器官中的有限积累来改善实体瘤的临床治疗。我们发现，低剂量节拍化疗对生长中的肿瘤血管内皮细胞和肿瘤细胞造成损伤，由于血管正常化和实体瘤中肿瘤内空间的扩大，增加了纳米载体的肿瘤积累。这一策略可能是基于纳米载体的抗癌药物在针对具有较低血管密度和渗透性的难治性肿瘤的抗癌化疗中的突破。

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.