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Mol Pharm. 2013 Mar 4;10(3):848-56. doi: 10.1021/mp300644n. Epub 2013 Feb 4.
The U.S. National Institutes of Health through the National Cancer Institute (NCI) have been charged with the goal of eliminating death and suffering from cancer by the year 2015. In order to achieve this very ambitious goal, the development of novel nanotechnology-based devices and therapeutics that are capable of one or more clinically important functions is envisioned. There is great hope and expectation in the development of theranostic nanocarriers, which combine diagnostic and therapeutic agents in one entity. Main delivery approaches include prodrugs, liposomes, polymersomes, and polymeric micelles and nanoparticles. Diagnostic and therapeutic agents are physically entrapped or conjugated to the nanocarriers, or they are conjugated to carefully designed polymers which subsequently form nanocarriers. This focus discusses pros and cons of the different theranostic approaches and tries to answer the question which approach has the highest probability to translate into the clinic and benefit patients. Carefully designed polymers, conjugated with diagnostic and therapeutic agents, that either self-assemble or can be processed to form nanocarriers offer clear advantages over random physical entrapment or conjugation of these agents to existing nanocarriers. These polymers can optionally be fitted with terminal stabilizing or anchoring functionalities and a targeting ligand. However, the need for nanocarriers that are subjected to the enhanced permeability and retention (EPR) effect to carry ligands for active targeting still needs to be demonstrated. Thirty-seven of the 41 nanocarrier-based formulations that are on the market or are under investigation at different levels of clinical development rely on passive targeting. The answer to the title question, not surprisingly, can only be no, but very promising approaches are being developed that have the potential to translate into the clinic and meet regulatory requirements.
美国国立卫生研究院(NIH)通过国家癌症研究所(NCI)负责在 2015 年之前消除癌症导致的死亡和痛苦。为了实现这一非常宏伟的目标,人们设想开发能够实现一种或多种临床重要功能的新型基于纳米技术的设备和疗法。在治疗诊断纳米载体的开发方面,人们寄予了很大的希望和期待,这种载体将诊断和治疗剂结合在一个实体中。主要的输送方法包括前药、脂质体、聚合物囊泡和聚合物胶束和纳米颗粒。诊断和治疗剂被物理包封或连接到纳米载体上,或者与精心设计的聚合物连接,随后形成纳米载体。本焦点讨论了不同治疗诊断方法的优缺点,并试图回答哪个方法最有可能转化为临床并使患者受益的问题。与将这些药物随机物理包封或连接到现有的纳米载体相比,与诊断和治疗药物连接的精心设计的聚合物可以自组装或经过处理形成纳米载体,具有明显的优势。这些聚合物可以选择配备末端稳定或锚定功能和靶向配体。然而,仍然需要证明需要纳米载体来利用增强的通透性和保留(EPR)效应来携带用于主动靶向的配体。市场上或在不同临床开发阶段正在研究的 41 种基于纳米载体的制剂中有 37 种依赖于被动靶向。标题问题的答案,不出所料,只能是否定的,但正在开发非常有前途的方法,有可能转化为临床并满足监管要求。
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