Department of Pharmaceutical Sciences, 19. South Manassas St., Memphis, TN 38103-3308, USA.
Adv Drug Deliv Rev. 2011 Jul 18;63(8):623-39. doi: 10.1016/j.addr.2010.11.005. Epub 2010 Dec 6.
Tumor microvasculature is fraught with numerous physiological barriers which hinder the efficacy of anticancer agents. These barriers include chaotic blood supply, poor tumor vasculature permeability, limited transport across the interstitium due to high interstitial pressure and absence of lymphatic network. Abnormal microvasculature also leads to hypoxia and acidosis which limits effectiveness of chemotherapy. These barriers restrict drug or drug carrier extravasation which hampers tumor regression. Targeting key features of the tumor microenvironment such as tumor microvessels, interstitial hypertension and tumor pH is a promising approach to improving the efficacy of anticancer drugs. This review highlights the current knowledge on the distinct tumor microenvironment generated barriers which limit extravasation of drugs and focuses on modalities for overcoming these barriers using multi-functional polymeric carriers. Special attention is given to utilizing polymeric nanomedicines to facilitate extravasation of anticancer drugs for future cancer therapy.
肿瘤微血管充满了许多生理屏障，这些屏障阻碍了抗癌药物的疗效。这些障碍包括血液供应紊乱、肿瘤血管通透性差、由于间质压力高导致跨间质的运输受限以及缺乏淋巴网络。异常的微血管还导致缺氧和酸中毒，从而限制了化疗的效果。这些障碍限制了药物或药物载体的渗出，从而阻碍了肿瘤的消退。针对肿瘤微环境的关键特征，如肿瘤微血管、间质高血压和肿瘤 pH 值，是提高抗癌药物疗效的一种有前途的方法。本文综述了目前关于限制药物渗出的独特肿瘤微环境生成障碍的知识，并重点介绍了使用多功能聚合物载体克服这些障碍的方法。特别关注利用聚合物纳米药物促进抗癌药物的渗出，以用于未来的癌症治疗。
