Nanocarriers as an Emerging Platform for Cancer Therapy
Nanocarriers as an Emerging Platform for Cancer Therapy
复制标题
DOI：
10.1201/9780429399039-2
复制
发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
D. Peer;J. Karp;Seungpyo Hong;O. Farokhzad;R. Margalit;R. Langer
中科院分区：
文献类型：
--
作者：
D. Peer;J. Karp;Seungpyo Hong;O. Farokhzad;R. Margalit;R. Langer
纳米技术有可能给癌症诊断和治疗带来革命性的变化。蛋白质工程和材料科学的进步为新的纳米级靶向方法做出了贡献，这可能会给癌症患者带来新的希望。几种治疗性纳米载体已被批准用于临床。然而，到目前为止，只有少数几个临床批准的纳米载体结合了选择性结合和靶向癌细胞的分子。本综述检查了一些已批准的配方，并讨论了将基础研究转化为临床所面临的挑战。我们详细介绍了可用于选择性肿瘤靶向的纳米载体和分子的武器库，并强调了癌症治疗中的挑战。癌症仍然是世界上最具破坏性的疾病之一，每年有1000多万新病例1。然而，由于对肿瘤生物学有了更好的了解以及诊断设备和治疗方法的改进，2死亡率在过去两年中有所下降。目前的癌症治疗方法包括手术干预、放射和化疗药物，这些药物通常也会杀死健康细胞，并对患者造成毒性。因此，开发能够被动或主动针对癌细胞的化疗药物是可取的。被动靶向利用了肿瘤生物学的特性，允许纳米载体通过增强的渗透性和滞留(EPR)效应在肿瘤中积累2。被动靶向纳米载体在20世纪80年代中期首次进入临床试验，第一批基于脂质体和聚合物-蛋白质结合物的产品于90年代中期上市。后来，基于这一策略的治疗性纳米载体被批准更广泛地使用(表1)，并研究了进一步增强药物对癌细胞靶向性的方法。主动方法通过将含有化疗药物的纳米载体与与靶细胞上过度表达的抗原或受体结合的分子结合来实现这一点。最近的综述提供了在癌症研究和纳米医学中使用纳米技术作为基本工具的前景3，4。在这里，我们集中于可以选择性靶向肿瘤的纳米载体和分子的潜力，并强调了将一些基础研究转化为临床所面临的挑战。被动和主动靶向纳米载体在到达其目标的途中遇到许多障碍，例如粘膜屏障和非特异性摄取5，6。为了应对利用纳米技术靶向肿瘤的挑战，有必要将纳米载体的合理设计与对肿瘤生物学的基本理解结合起来(方框1)。肿瘤的一般特征包括血管渗漏和淋巴引流不良。虽然免费药物可以非特异性地扩散，但纳米载体可以…
Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment. Cancer remains one of the world's most devastating diseases, with more than 10 million new cases every year 1. However, mortality has decreased in the past two years 2 owing to better understanding of tumour biology and improved diagnostic devices and treatments. Current cancer treatments include surgical intervention, radiation and chemotherapeutic drugs, which often also kill healthy cells and cause toxicity to the patient. It would therefore be desirable to develop chemotherapeutics that can either passively or actively target cancerous cells. Passive targeting exploits the characteristic features of tumour biology that allow nanocarriers to accumulate in the tumour by the enhanced permeability and retention (EPR) effect 2. Passively targeting nanocarriers first reached clinical trials in the mid-1980s, and the first products, based on liposomes and polymer–protein conjugates, were marketed in the mid-1990s. Later, therapeutic nanocarriers based on this strategy were approved for wider use (Table 1) and methods of further enhancing targeting of drugs to cancer cells were investigated. Active approaches achieve this by conjugating nanocarriers containing chemotherapeutics with molecules that bind to overexpressed antigens or receptors on the target cells. Recent reviews provide perspective on the use of nanotechnology as a fundamental tool in cancer research and nanomedicine 3,4. Here we focus on the potential of nanocarriers and molecules that can selectively target tumours, and highlight the challenges in translating some of the basic research to the clinic. PaSSive anD aCtive targeting Nanocarriers encounter numerous barriers en route to their target, such as mucosal barriers and non-specific uptake 5,6. To address the challenges of targeting tumours with nanotechnology, it is necessary to combine the rational design of nanocarriers with the fundamental understanding of tumour biology (Box 1). General features of tumours include leaky blood vessels and poor lymphatic drainage. Whereas free drugs may diffuse non-specifically, a nanocarrier can …