Kutova Olga M, Guryev Evgenii L, Sokolova Evgeniya A, Alzeibak Razan, Balalaeva Irina V
The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., Nizhny Novgorod 603950, Russia.
The Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, 8-2 Trubetskaya str., Moscow 119991, Russia.
Cancers (Basel). 2019 Jan 10;11(1):68. doi: 10.3390/cancers11010068.
Malignant tumors are characterized by structural and molecular peculiarities providing a possibility to directionally deliver antitumor drugs with minimal impact on healthy tissues and reduced side effects. Newly formed blood vessels in malignant lesions exhibit chaotic growth, disordered structure, irregular shape and diameter, protrusions, and blind ends, resulting in immature vasculature; the newly formed lymphatic vessels also have aberrant structure. Structural features of the tumor vasculature determine relatively easy penetration of large molecules as well as nanometer-sized particles through a blood⁻tissue barrier and their accumulation in a tumor tissue. Also, malignant cells have altered molecular profile due to significant changes in tumor cell metabolism at every level from the genome to metabolome. Recently, the tumor interaction with cells of immune system becomes the focus of particular attention, that among others findings resulted in extensive study of cells with preferential tropism to tumor. In this review we summarize the information on the diversity of currently existing approaches to targeted drug delivery to tumor, including (i) passive targeting based on the specific features of tumor vasculature, (ii) active targeting which implies a specific binding of the antitumor agent with its molecular target, and (iii) cell-mediated tumor targeting.
恶性肿瘤具有结构和分子特性，这使得定向递送抗肿瘤药物成为可能，同时对健康组织的影响最小且副作用减少。恶性病变中新形成的血管呈现出杂乱的生长、无序的结构、不规则的形状和直径、凸起及盲端，导致血管系统不成熟；新形成的淋巴管结构也异常。肿瘤血管系统的结构特征决定了大分子以及纳米级颗粒相对容易穿透血组织屏障并在肿瘤组织中蓄积。此外，由于从基因组到代谢组的各个水平上肿瘤细胞代谢发生显著变化，恶性细胞的分子特征也发生了改变。最近，肿瘤与免疫系统细胞的相互作用成为特别受关注的焦点，这一发现引发了对具有肿瘤优先嗜性的细胞的广泛研究。在这篇综述中，我们总结了目前现有的肿瘤靶向药物递送方法的多样性信息，包括：（i）基于肿瘤血管系统特定特征的被动靶向；（ii）意味着抗肿瘤剂与其分子靶点特异性结合的主动靶向；以及（iii）细胞介导的肿瘤靶向。
