Cancer Drug Delivery: Considerations in the Rational Design of Nanosized Bioconjugates
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- 作者：Hisataka Kobayashi ; Baris Turkbey ; Rira Watanabe ; Peter L. Choyke
- 刊名：Bioconjugate Chemistry
- 出版年：2014
- 出版时间：December 17, 2014
- 年：2014
- 卷：25
- 期：12
- 页码：2093-2100
- 全文大小：362K
- ISSN：1520-4812
文摘
In order to efficiently deliver anticancer agents to tumors, biocompatible nanoparticles or bioconjugates, including antibody鈥揹rug conjugates (ADCs), have recently been designed, synthesized, and tested, some even in clinical trials. Controlled delivery can be enhanced by changing specific design characteristics of the bioconjugate such as its size, the nature of the payload, and the surface features. The delivery of macromolecular drugs to cancers largely relies on the leaky nature of the tumor vasculature compared with healthy vessels in normal organs. When administered intravenously, macromolecular bioconjugates and nanosized agents tend to circulate for prolonged times, unless they are small enough to be excreted by the kidney or stealthy enough to evade the macrophage phagocytic system (MPS), formerly the reticulo-endothelial system (RES). Therefore, macromolecular bioconjugates and nanosized agents with long circulation times leak preferentially into tumor tissue through permeable tumor vessels and are then retained in the tumor bed due to reduced lymphatic drainage. This process is known as the enhanced permeability and retention (EPR) effect. However, success of cancer drug delivery only relying on the EPR effect is still limited. To cure cancer patients, further improvement of drug delivery is required by both designing superior agents and enhancing EPR effects. In this Review, we describe the basis of macromolecular or nanosized bioconjugate delivery into cancer tissue and discuss current diagnostic methods for evaluating leakiness of the tumor vasculature. Then, we discuss methods to augment conventional 鈥減ermeability and retention鈥?effects for macromolecular or nanosized bioconjugates in cancer tissue.