Center for Biomimetic Medicine, Houston Methodist Research Institute, Houston, TX, 77030, United States.
Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, United States.
Curr Med Chem. 2018;25(34):4208-4223. doi: 10.2174/0929867324666170920160030.
Cancer treatment still remains a challenge due to the several limitations of currently used chemotherapeutics, such as their poor pharmacokinetics, unfavorable chemical properties, as well as inability to discriminate between healthy and diseased tissue. Nanotechnology offered potent tools to overcome these limitations. Drug encapsulation within a delivery system permitted i) to protect the payload from enzymatic degradation/ inactivation in the blood stream, ii) to improve the physicochemical properties of poorly water-soluble drugs, like paclitaxel, and iii) to selectively deliver chemotherapeutics to the cancer lesions, thus reducing the off-target toxicity, and promoting the intracellular internalization. To accomplish this purpose, several strategies have been developed, based on biological and physical changes happening locally and systemically as a consequence of tumorigenesis. Here, we will discuss the role of inflammation in the different steps of tumor development and the strategies based on the use of nanoparticles that exploit the inflammatory pathways in order to selectively target the tumor-associated microenvironment for therapeutic and diagnostic purposes.
由于目前使用的化疗药物存在多种局限性,如药代动力学不佳、化学性质不理想以及无法区分健康组织和病变组织,癌症治疗仍然是一个挑战。纳米技术为克服这些局限性提供了有力的工具。将药物封装在递送系统中可以:i)保护有效载荷免受血液中酶的降解/失活,ii)改善紫杉醇等水溶性差的药物的物理化学性质,iii)选择性地将化疗药物递送到癌症病灶,从而降低脱靶毒性并促进细胞内内化。为了实现这一目的,已经开发了基于生物和物理变化的几种策略,这些变化是由于肿瘤发生而在局部和全身范围内发生的。在这里,我们将讨论炎症在肿瘤发展的不同阶段的作用,以及基于利用炎症途径的纳米粒子策略,以便有针对性地治疗和诊断肿瘤相关的微环境。