Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Curr Med Chem. 2013;20(23):2881-91. doi: 10.2174/09298673113209990004.
In recent decades, nanoparticulate drug delivery systems have attracted extensive attention in cancer therapy for such appealing properties as small particle size, huge surface area, narrow size distribution and prolonged circulation time. Although several nanomedicines have successfully reached the clinical, evidences have proved that therapeutic efficacy isn't improved significantly, except for better toleration and less side effects. Given that the physiological abnormalities in tumors, multiple biobarriers need to be overcome before nanomedicines are delivered to the target site. Passive targeting nanoparticles ensure nanomedicines' extensive extravasation from tumor vessels via enhanced permeation and retention effect, but the diffusion distance is limited to 2-3 cell layer thicknesses. Active targeting nanoparticles tend to bind the peripheral cells of the tumor mass, hindering nanoparticles further penetration into the tumor core region. Therefore, how to improve the deep penetration of nanomedicines into tumors is a formidable task for achieving the desired anticancer therapeutic efficacy. This review demonstrates the penetration obstacles existing in tumor region for nanoparticles, summarizes the important properties of nanomedicines affecting tumor deep penetration and highlights the solutions to improve tumor deep penetration of nanoparticles.
近几十年来，纳米颗粒药物递送系统因其小粒径、大表面积、窄粒径分布和延长的循环时间等诱人特性，在癌症治疗中引起了广泛关注。尽管有几种纳米药物已经成功进入临床，但有证据表明，除了更好的耐受性和更少的副作用外，治疗效果并没有显著提高。鉴于肿瘤中的生理异常，纳米药物需要克服多个生物屏障才能递送到靶部位。被动靶向纳米颗粒通过增强渗透和保留效应确保纳米药物从肿瘤血管中广泛渗出，但扩散距离仅限于 2-3 个细胞层的厚度。主动靶向纳米颗粒倾向于与肿瘤团块的外周细胞结合，阻碍纳米颗粒进一步渗透到肿瘤核心区域。因此，如何提高纳米药物进入肿瘤的深度渗透是实现理想抗癌治疗效果的一项艰巨任务。本文综述了纳米颗粒在肿瘤区域存在的渗透障碍，总结了影响纳米药物肿瘤深层渗透的重要性质，并强调了提高纳米颗粒肿瘤深层渗透的解决方案。
