Markedly Enhanced Permeability and Retention Effects Induced by Photo-immunotherapy of Tumors
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- 作者：Kohei Sano ; Takahito Nakajima ; Peter L. Choyke ; Hisataka Kobayashi
- 刊名：ACS Nano
- 出版年：2013
- 出版时间：January 22, 2013
- 年：2013
- 卷：7
- 期：1
- 页码：717-724
- 全文大小：551K
- 年卷期：v.7,no.1(January 22, 2013)
- ISSN：1936-086X
文摘
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鈥損hotosensitizer conjugate, there was surprisingly high leakage of nanosized (10鈥?00 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 nanomaterials within the PIT-treated tumor compared with controls, an effect termed 鈥渟uper-enhanced permeability and retention鈥? 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.