Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
Acc Chem Res. 2011 Oct 18;44(10):853-62. doi: 10.1021/ar2000277. Epub 2011 Apr 29.
Nanotechnology provides a flexible platform for the development of effective therapeutic nanomaterials that can interact specifically with a target in a biological system and provoke a desired response. Of the nanomaterials studied, iron oxide nanoparticles have emerged as one of top candidates for cancer therapy. Their intrinsic superparamagnetism enables noninvasive magnetic resonance imaging (MRI), and their biodegradability is advantageous for in vivo applications. A therapeutic superparamagnetic iron oxide nanoparticle (SPION) typically consists of three primary components: an iron oxide nanoparticle core that serves as both a carrier for therapeutics and contrast agent for MRI, a coating on the iron oxide nanoparticle that promotes favorable interactions between the SPION and the biological system, and a therapeutic payload that performs the designated function in vivo. Often, the design may include a targeting ligand that recognizes the receptors over-expressed on the exterior surface of cancer cells. The body is a highly complex system that imposes multiple physiological and cellular barriers to foreign objects. Thus, the success of a therapeutic SPION largely relies on the design of the iron oxide core to ensure its detection in MRI and the coatings that allow the nanoparticles to bypass these barriers. Strategies to bypass the physiological barriers, such as liver, kidneys, and spleen, involve tuning the overall size and surface chemistry of the SPION to maximize blood half-life and facilitate the navigation in the body. Strategies to bypass cellular barriers include the use of targeting agents to maximize uptake of the SPION by cancer cells and the employment of materials that promote desired intracellular trafficking and enable controlled drug release. The payload can be genes, proteins, chemotherapy drugs, or a combination of these molecules. Each type of therapeutic molecule requires a specific coating design to maximize the loading and to achieve effective delivery and release. In this Account, we discuss the primary design parameters in developing therapeutic SPIONs with a focus on surface coating design to overcome the barriers imposed by the body's defense system. We provide examples of how these design parameters have been implemented to produce SPIONs for specific therapeutic applications. Although there are still challenges to be addressed, SPIONs show great promise in the successful diagnosis and treatment of the most devastating cancers. Once the critical design parameters have been optimized, these nanoparticles, combined with imaging modalities, can serve as truly multifunctional theranostic agents that not only perform a therapeutic function but also provide instant clinical feedback, allowing the physician to adjust the treatment plan.
纳米技术为开发能够与生物系统中的靶标特异性相互作用并引发所需反应的有效治疗性纳米材料提供了一个灵活的平台。在研究的纳米材料中，氧化铁纳米颗粒已成为癌症治疗的首选候选材料之一。其固有超顺磁性能够实现非侵入性磁共振成像（MRI），并且其生物降解性有利于体内应用。治疗超顺磁性氧化铁纳米颗粒（SPION）通常由三个主要成分组成：作为治疗药物载体和 MRI 对比剂的氧化铁纳米颗粒核心、促进 SPION 与生物系统之间有利相互作用的氧化铁纳米颗粒涂层，以及在体内执行指定功能的治疗有效载荷。通常，设计可能包括识别癌细胞外表面过表达的受体的靶向配体。人体是一个高度复杂的系统，对外来物体施加多种生理和细胞屏障。因此，治疗性 SPION 的成功在很大程度上取决于氧化铁核心的设计，以确保其在 MRI 中的检测，以及允许纳米颗粒绕过这些屏障的涂层。为了绕过生理屏障，如肝脏、肾脏和脾脏，需要调整 SPION 的整体尺寸和表面化学性质，以最大限度地延长血液半衰期并促进体内导航。为了绕过细胞屏障，包括使用靶向剂使 SPION 最大限度地被癌细胞摄取，以及使用促进所需细胞内运输并实现受控药物释放的材料。有效载荷可以是基因、蛋白质、化疗药物或这些分子的组合。每种类型的治疗分子都需要特定的涂层设计来最大限度地提高负载量并实现有效的递药和释放。在本综述中，我们讨论了开发治疗性 SPION 的主要设计参数，重点是表面涂层设计，以克服身体防御系统施加的障碍。我们提供了如何实施这些设计参数来生产用于特定治疗应用的 SPION 的示例。尽管仍存在待解决的挑战，但 SPION 在成功诊断和治疗最具破坏性的癌症方面显示出巨大的潜力。一旦优化了关键设计参数，这些纳米颗粒与成像方式相结合，可以作为真正的多功能治疗诊断剂，不仅具有治疗功能，还能提供即时的临床反馈，使医生能够调整治疗计划。
