Center for Bionanoengineering and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310007, China.
Brain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing Laboratory of Biomedical Materials Beijing, 100070, PR China.
Biomaterials. 2020 May;240:119902. doi: 10.1016/j.biomaterials.2020.119902. Epub 2020 Feb 18.
Nanotechnology-based drug delivery platforms have been explored for cancer treatments and resulted in several nanomedicines in clinical uses and many in clinical trials. However, current nanomedicines have not met the expected clinical therapeutic efficacy. Thus, improving therapeutic efficacy is the foremost pressing task of nanomedicine research. An effective nanomedicine must overcome biological barriers to go through at least five steps to deliver an effective drug into the cytosol of all the cancer cells in a tumor. Of these barriers, nanomedicine extravasation into and infiltration throughout the tumor are the two main unsolved blockages. Up to now, almost all the nanomedicines are designed to rely on the high permeability of tumor blood vessels to extravasate into tumor interstitium, i.e., the enhanced permeability and retention (EPR) effect or so-called "passive tumor accumulation"; however, the EPR features are not so characteristic in human tumors as in the animal tumor models. Following extravasation, the large size nanomedicines are almost motionless in the densely packed tumor microenvironment, making them restricted in the periphery of tumor blood vessels rather than infiltrating in the tumors and thus inaccessible to the distal but highly malignant cells. Recently, we demonstrated using nanocarriers to induce transcytosis of endothelial and cancer cells to enable nanomedicines to actively extravasate into and infiltrate in solid tumors, which led to radically increased anticancer activity. In this perspective, we make a brief discussion about how active transcytosis can be employed to overcome the difficulties, as mentioned above, and solve the inherent extravasation and infiltration dilemmas of nanomedicines.
基于纳米技术的药物递送平台已被探索用于癌症治疗，并导致几种纳米药物在临床应用和许多在临床试验中。然而，目前的纳米药物尚未达到预期的临床治疗效果。因此，提高治疗效果是纳米医学研究的首要紧迫任务。一种有效的纳米药物必须克服生物屏障，至少要经过五个步骤才能将有效药物递送到肿瘤中所有癌细胞的细胞质中。在这些障碍中，纳米药物渗透到肿瘤内部并渗透到整个肿瘤是两个主要未解决的障碍。到目前为止，几乎所有的纳米药物都被设计为依赖于肿瘤血管的高通透性来渗透到肿瘤间质中，即增强的通透性和保留（EPR）效应或所谓的“被动肿瘤积累”；然而，EPR 特征在人类肿瘤中并不像在动物肿瘤模型中那么典型。在渗透之后，大尺寸的纳米药物在密集堆积的肿瘤微环境中几乎处于静止状态，使它们局限于肿瘤血管的外围，而不是渗透到肿瘤中，因此无法到达远端但高度恶性的细胞。最近，我们通过使用纳米载体诱导内皮细胞和癌细胞的转胞吞作用，使纳米药物能够主动渗透到实体瘤中并渗透到其中，从而大大提高了抗癌活性。在这篇观点文章中，我们简要讨论了主动转胞吞作用如何能够克服上述困难，并解决纳米药物固有的渗透和渗透困境。
