文章：

癌症纳米医学：进展、挑战和机遇

Cancer nanomedicine: progress, challenges and opportunities

原文发布日期：2016-11-11

DOI: 10.1038/nrc.2016.108

类型: Review Article

开放获取: 否

要点：

1. Although first-generation cancer nanomedicines have been in clinical practice for more than 20 years, the total number of papers related to 'nanoparticle' on PubMed nearly doubled every 2 years between 2000 and 2014, and more than half of the papers on nanoparticles have been published in the past 5 years, indicating that our knowledge and arsenal of cancer nanomedicines is rapidly expanding.
2. Cancer nanomedicines accumulate in solid tumours through the enhanced permeability and retention (EPR) effect, which is increasingly appreciated to be complex, dynamic and heterogeneous across tumours and even within the same tumour.
3. Identifying biomarkers for the EPR effect may enable selection of cancer patients most likely to benefit from nanotherapeutics, prompting the development of personalized nanomedicine.
4. Effective systemic delivery of nanotherapeutics to solid tumours requires a deeper understanding of the biological factors involved, such as nanoparticle–protein interaction, blood circulation, extravasation to and interaction with the perivascular tumour microenvironment (TME), tumour tissue penetration, tumour cell internalization and intracellular trafficking.
5. The physicochemical properties of nanotherapeutics (for example, size, geometry, surface features, elasticity, stiffness, porosity, composition, targeting ligand and drug release kinetics) affect systemic delivery to tumours, thus determining the EPR effect and therapeutic outcomes.
6. Targeting the TME and the premetastatic niche with nanotechnologies offers another promising strategy for cancer therapy.
7. Addressing the challenges of controllable, reproducible and scalable nanoparticle synthesis will facilitate the clinical translation of cancer nanomedicines.

要点翻译：

1. 尽管第一代癌症纳米药物进入临床实践已超过20年，但PubMed数据库中与"纳米颗粒"相关的论文总数在2000年至2014年间约每两年翻一番，其中超过半数论文发表于过去五年，这表明我们对癌症纳米药物的认知体系正在快速扩展。
2. 癌症纳米药物通过增强渗透与滞留（EPR）效应在实体瘤中富集，该效应日益被认识到具有复杂性、动态性特征，且在不同肿瘤乃至同一肿瘤内部存在高度异质性。
3. 识别EPR效应的生物标志物或可筛选最可能从纳米疗法中获益的癌症患者，推动个体化纳米医学的发展。
4. 实现纳米疗法对实体瘤的有效系统递送，需要深入理解相关生物学因素，包括纳米颗粒-蛋白质相互作用、血液循环、血管外渗、血管周围肿瘤微环境（TME）的相互作用、肿瘤组织渗透、肿瘤细胞内化及细胞内运输。
5. 纳米疗法的物理化学特性（如尺寸、几何形态、表面特征、弹性、硬度、孔隙率、组成成分、靶向配体和药物释放动力学）影响肿瘤的系统性递送效率，从而决定EPR效应及治疗结局。
6. 利用纳米技术靶向TME与转移前微环境为癌症治疗提供了新策略。
7. 解决纳米颗粒可控合成、批次重现性与规模化制备的挑战，将加速癌症纳米药物的临床转化。

英文摘要：

The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano–bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano–bio interactions to develop more effective nanotherapeutics for cancer patients.

摘要翻译： 

传统癌症疗法的固有限限促使人们开发并应用多种纳米技术，以实现更有效、更安全的癌症治疗，即所谓的“癌症纳米医学”。该领域已取得显著的技术突破，但纳米医学要成为癌症治疗新范式，仍面临肿瘤生物学复杂性与异质性、纳米-生物相互作用认知不足，以及临床转化和商业化所需的化学、制造与质量控制等挑战。本综述梳理了癌症纳米医学的进展、挑战与机遇，并探讨了新兴工程策略，这些策略利用我们对肿瘤生物学和纳米-生物相互作用日益深入的理解，以开发更高效的纳米治疗药物，造福癌症患者。

原文链接：

Cancer nanomedicine: progress, challenges and opportunities