Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
J Control Release. 2021 May 10;333:418-447. doi: 10.1016/j.jconrel.2021.03.045. Epub 2021 Apr 1.
Tumor-sensitivity, effective transport, and precise delivery to tumor cells of nano drug delivery systems (NDDs) have been great challenges to cancer therapy in recent years. The conventional targeting approach involves actively installing the corresponding ligand on the nanocarriers, which is prone to recognize the antigen blasts overexpressed on the surface of tumor cells. However, there are some probable limitations for the active tumor-targeting systems in vivo as follows: a. the limited ligand amount of modifications; b. possible steric hindrance, which was likely to prevent ligand-receptor interaction during the delivery process. c. the restrained antigen saturation highly expressed on the cell membrane, will definitely decrease the specificity and often lead to "off-target" effects of NDDs; and d. water insolubility of nanocarriers due to excess of ligands modification. Obviously, any regulation of receptors on surface of tumor cells exerted an important influence on the delivery of targeting systems. Herein, receptor upregulation was mostly desired for enhancing targeted therapy from the cellular level. This technique with the amplification of receptors has the potential to enhance tumor sensitivity towards corresponding ligand-modified nanoparticles, and thereby increasing the effective therapeutic concentration as well as improving the efficacy of chemotherapy. The enhancement of positively expressed receptors on tumor cells and receptor-dependent therapeutic agents or NDDs with an assembled "self-promoting" effect contributes to increasing cell sensitivity to NPs, and will provide a basic platform for clinical therapeutic practice. In this review, we highlight the significance of modulating various receptors on different types of cancer cells for drug delivery and therapeutic benefits.
近年来，纳米药物递送系统（NDDs）对肿瘤细胞的肿瘤敏感性、有效传输和精确递药一直是癌症治疗的重大挑战。传统的靶向方法涉及在纳米载体上主动安装相应的配体，这容易识别肿瘤细胞表面过表达的抗原。然而，主动肿瘤靶向系统在体内可能存在一些局限性，如下：a. 修饰配体的数量有限；b. 可能的空间位阻，这可能会在递药过程中阻止配体-受体相互作用；c. 细胞膜上高度表达的抗原饱和，这肯定会降低特异性，并且常常导致 NDDs 的“脱靶”效应；d. 纳米载体的水不溶性由于修饰配体过多。显然，肿瘤细胞表面受体的任何调节都对靶向系统的递药有重要影响。在此，从细胞水平增强靶向治疗，受体上调是大多数人所期望的。这种技术通过受体的放大，有可能增强肿瘤对相应配体修饰纳米颗粒的敏感性，从而增加有效治疗浓度，提高化疗效果。增加肿瘤细胞上阳性表达受体和受体依赖性治疗剂或具有组装“自我促进”效应的 NDDs，有助于提高细胞对 NPs 的敏感性，为临床治疗实践提供了一个基本平台。在这篇综述中，我们强调了调节不同类型癌细胞上各种受体对药物输送和治疗益处的重要性。
