Polymeric Nanostructures for Imaging and Therapy.
Polymeric Nanostructures for Imaging and Therapy.
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DOI：
10.1021/acs.chemrev.5b00135
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发表时间：
2015-10-14
期刊：
影响因子：
62.1
通讯作者：
Wooley KL
中科院分区：
文献类型：
--
作者：
Elsabahy M;Heo GS;Lim SM;Sun G;Wooley KL
医学诊断和治疗对于为患者提供适当的护理至关重要，尽管无效的诊断和治疗通常与疾病的不正确检测、不满意的治疗结果和/或严重的不良反应有关。各种诊断和治疗剂的设计进展，以及利用分子用于治疗和诊断应用（即，治疗诊断学）的最近趋势，仍然没有实现控制这些分子在生物系统内的导航和生物分布的最大益处。使用这些药物的关键挑战，从小分子到大分子药物（例如，基于天然、蛋白质和核酸的药物，或合成的、基于聚合物的缀合物、载体或其它系统），例如，通过快速清除或降解而丧失活性，向靶位点的低效递送，以及疾病状态的不适当探测，这取决于特定的疾病及其在体内的位置。纳米技术的概念于1959年初由理查德·费曼（Richard Feynman）在加州理工学院著名的历史演讲“底部有足够的空间”中提出，并引入了在原子和分子水平上操纵材料的可能性。(1)1974年，东京大学的谷口纪夫（Norio Taniguchi）首次使用了“纳米技术”一词，指的是纳米级材料的设计。(2)从20世纪90年代初到现在，不同性质（有机和无机）的纳米材料在各种应用（多学科）中的使用已经大大扩展，特别是在过去几十年中。（3，4）在医学领域，纳米技术已经出现，包括用于探测疾病的非侵入性系统，并且还能够携带用于局部高浓度递送的货物，称为“纳米医学”，减少脱靶效应。纳米材料，特别是聚合物纳米结构的使用已经证明了在改善诊断剂和治疗剂向靶位点的递送方面的效率，以及在纳米颗粒的特定隔室内掺入几种治疗/诊断/靶向部分的可行性，并控制其在体内和靶位点的导航。进一步了解生物系统的性质和微环境（例如，不同的pH值，温度，渗透性，排水或过度表达蛋白质，酶或受体），以及将各种部分递送到其目的地的障碍，这些障碍可以是内部或外部的，有助于设计可以避开各种生理障碍的纳米材料。选择性地输送到疾病部位可以提高治疗效果、成像对比度和准确性，同时减少不良反应以及药物的剂量和成本，最初，平台技术是纳米结构设计的目标，但随着生物系统的复杂化，在过去的十年中，人们已经认识到，需要针对疾病和患者的特定医学治疗才能获得疗效-本文综述了近几年来发展起来的几个例子，重点介绍了体内研究以及新的设计和合成方面的重大进展。聚合物纳米结构相对于其他类型纳米材料的优势是基于其结构可以被修改以产生各种组成，形态，尺寸和表面性质的材料的灵活性，具有将各种组分的几种纳米材料分层组装成一种结构的可能性，该结构可以适应各种治疗，诊断和治疗。
Medical diagnosis and therapy are essential for providing patients with proper care, although inefficient diagnosis and therapy are usually associated with either improper detection of the diseases, unsatisfactory therapeutic outcomes, and/or serious adverse reactions. Advances in the design of various diagnostic and therapeutic agents, and the recent trend of utilizing molecules for both therapeutic and diagnostic applications (ie, theranostics), still have not achieved the maximum benefits of controlling the navigation and biodistribution of these molecules within the biological system. The key challenges toward the use of these agents, from small molecules to macromolecular drugs (eg, natural, proteins, and nucleic acids-based drugs, or synthetic, polymer-based conjugates, carriers, or other systems), are, for example, the loss of activity via rapid clearance or degradation, inefficient delivery to the target sites, and inappropriate probing of the disease states, dependent on the particular disease and its location in the body. The concept of nanotechnology was initiated early in 1959 by Richard Feynman in his famous historical talk at Caltech “There’s Plenty of Room at the Bottom”, with introduction of the possibility of manipulating materials at the atomic and molecular levels.(1) In 1974, Norio Taniguchi, at Tokyo University, first utilized the term “nanotechnology”, referring to the design of materials on the nanoscale.(2) In the early 1990s and until now, the use of nanomaterials of different natures (organic and inorganic) and for various applications (multiple disciplines) has been greatly expanded, in particular over the last couple of decades.(3, 4) In the medical field, nanotechnology has emerged to include noninvasive systems for probing of disease and is also capable of carrying cargo for localized high concentration delivery, known as “nanomedicine”, with reduction of off-target effects. The use of nanomaterials, in particular polymeric nanostructures, has demonstrated efficiency in improving delivery of diagnostic and therapeutic agents to the target sites, and the feasibility of incorporating several therapeutic/diagnostic/targeting moieties within specific compartments of the nanoparticles, with control of their navigation in the body and to the target sites. Further understanding of the nature and microenvironments of biological systems (eg, different pH, temperature, permeability, drainage, or overexpressing proteins, enzymes, or receptors), and the barriers toward the delivery of various moieties to their destinations, which could be either intra-or extracellular, has aided the design of nanomaterials that could evade the various physiological barriers. Selective delivery to the site of the disease can increase the therapeutic efficacy, imaging contrast, and accuracy, while reducing adverse reactions and the dose and cost of medications.Initially, platform technologies were the target for nanostructure designs, but with the complications of biological systems, it has been recognized over the past decade that disease-and patient-specific medical treatment is needed for efficacy—this review highlights a few examples developed within the past couple of years, with a focus on in vivo studies together with novel designs and significant advances in syntheses. The advantages of polymeric nanostructures over other types of nanomaterials are based upon the flexibility over which their structures can be modified to yield materials of various compositions, morphologies, sizes, and surface properties, with the possibility of hierarchical assembly of several nanomaterials of various components into one construct that can be accommodated with a variety of therapeutic, diagnostic, and …