The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery-Personal Remarks and Future Prospects.
The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery-Personal Remarks and Future Prospects.
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DOI：
10.3390/jpm11030229
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发表时间：
2021-03-22
影响因子：
--
通讯作者：
Maeda H
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文献类型：
--
作者：
Maeda H
这期关于增强渗透性和保留（EPR）效应的特刊纪念其发现35周年，1986年Matsumura和Maeda的发现作为癌症化疗的新概念发表在Cancer Research上。我的评论在这里描述了EPR效应的历史和异质性，这涉及到有缺陷的肿瘤血管和血流。我们报道了恢复阻塞的肿瘤血流克服了受损的药物递送，从而改善了EPR效应。我还讨论了实验模型中使用的小动物癌症和人类的大型临床癌症之间的差距，这通常涉及异质性EPR效应，多个坏死灶中的血管异常和肿瘤栓塞。在这里，我强调将纳米药物油性制剂经动脉输注到肿瘤供血动脉中，这是对肿瘤选择性最强的药物递送方法，肿瘤/血液比为100倍。这种方法实际上是最个性化的药物，因为每个患者的动脉输注不同，输注的药物剂量取决于每个患者的肿瘤大小和解剖结构。EPR效应治疗的未来发展将从化疗到光动力治疗、硼中子捕获治疗和自由基疾病治疗。这篇综述着重于我们自己的工作，这激发了众多科学家在纳米技术和药物输送系统方面的研究，从而催生了一个新的癌症治疗时代。
This Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in Cancer Research as a new concept in cancer chemotherapy. My review here describes the history and heterogeneity of the EPR effect, which involves defective tumor blood vessels and blood flow. We reported that restoring obstructed tumor blood flow overcomes impaired drug delivery, leading to improved EPR effects. I also discuss gaps between small animal cancers used in experimental models and large clinical cancers in humans, which usually involve heterogeneous EPR effects, vascular abnormalities in multiple necrotic foci, and tumor emboli. Here, I emphasize arterial infusion of oily formulations of nanodrugs into tumor-feeding arteries, which is the most tumor-selective drug delivery method, with tumor/blood ratios of 100-fold. This method is literally the most personalized medicine because arterial infusions differ for each patient, and drug doses infused depend on tumor size and anatomy in each patient. Future developments in EPR effect-based treatment will range from chemotherapy to photodynamic therapy, boron neutron capture therapy, and therapies for free radical diseases. This review focuses on our own work, which stimulated numerous scientists to perform research in nanotechnology and drug delivery systems, thereby spawning a new cancer treatment era.
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