Markedly enhanced permeability and retention effects induced by photo-immunotherapy of tumors.
Markedly enhanced permeability and retention effects induced by photo-immunotherapy of tumors.
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DOI：
10.1021/nn305011p
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发表时间：
2013-01-22
期刊：
影响因子：
17.1
通讯作者：
Kobayashi, Hisataka
中科院分区：
文献类型：
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作者：
Sano, Kohei;Nakajima, Takahito;Choyke, Peter L.;Kobayashi, Hisataka
关键词：
癌症治疗的一个主要障碍是无法在不引起全身毒性的情况下将足够浓度的药物输送到肿瘤。纳米材料很有吸引力，因为它们可以携带大量的药物，然而，肿瘤的传递受到大多数肿瘤适度渗漏和滞留的限制。我们观察到，经过光免疫疗法(PIT)，这是一种基于抗体-光敏剂结合物的光介导性治疗，有令人惊讶的高渗漏纳米尺寸(10-200 nm)的试剂进入肿瘤床。PIT迅速导致血管周围癌细胞死亡，导致血管通透性立即和显著增加，导致经PIT治疗的肿瘤内纳米非肿瘤物质的积聚比对照组增加多达24倍，这种效应被称为“超级增强的渗透性和滞留”(SUPR)。在一项治疗研究中，与单独使用PIT或DaunoXome相比，PIT和含有柔红霉素的脂质体DaunoXome(直径50 nm)在荷瘤小鼠中的存活率更高。因此，PIT极大地增强了纳米试剂的输送，从而有望改善治疗反应。
A major barrier to cancer treatment is the inability to deliver sufficient concentrations of drug to the tumor without incurring systemic toxicities. Nanomaterials are appealing because they can carry a large drug payload, however, tumor delivery is limited by modest leakage and retention in most tumors. We observed that after photoimmunotherapy (PIT), which is a light mediated treatment based on an antibody-photosensitizer conjugate, there was surprisingly high leakage of nanosized (10–200 nm) agents into the tumor bed. PIT rapidly induced death in perivascular cancer cells leading to immediate and dramatic increases in vascular permeability resulting in up to 24-fold greater accumulation of nanonanomaterials within the PIT-treated tumor compared with controls, an effect termed “super-enhanced permeability and retention” (SUPR). In a treatment study, PIT followed by liposome-containing daunorubicin, DaunoXome (diameter 50 nm), resulted in greater survival in tumor-bearing mice than either PIT or DaunoXome alone. Thus, PIT greatly enhances delivery of nanosized reagents and thus holds promise to improve therapeutic responses.
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