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肝素及基于肝素的药物递送系统:对骨肉瘤和免疫细胞多药耐药性的多效性分子效应

Heparin and Heparin-Based Drug Delivery Systems: Pleiotropic Molecular Effects at Multiple Drug Resistance of Osteosarcoma and Immune Cells.

作者信息

Todosenko Natalia, Yurova Kristina, Khaziakhmatova Olga, Malashchenko Vladimir, Khlusov Igor, Litvinova Larisa

机构信息

Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia.

Department of Morphology and General Pathology, Siberian State Medical University, 634050 Tomsk, Russia.

出版信息

Pharmaceutics. 2022 Oct 13;14(10):2181. doi: 10.3390/pharmaceutics14102181.

Abstract

One of the main problems of modern health care is the growing number of oncological diseases both in the elderly and young population. Inadequately effective chemotherapy, which remains the main method of cancer control, is largely associated with the emergence of multidrug resistance in tumor cells. The search for new solutions to overcome the resistance of malignant cells to pharmacological agents is being actively pursued. Another serious problem is immunosuppression caused both by the tumor cells themselves and by antitumor drugs. Of great interest in this context is heparin, a biomolecule belonging to the class of glycosaminoglycans and possessing a broad spectrum of biological activity, including immunomodulatory and antitumor properties. In the context of the rapid development of the new field of "osteoimmunology," which focuses on the collaboration of bone and immune cells, heparin and delivery systems based on it may be of intriguing importance for the oncotherapy of malignant bone tumors. Osteosarcoma is a rare but highly aggressive, chemoresistant malignant tumor that affects young adults and is characterized by constant recurrence and metastasis. This review describes the direct and immune-mediated regulatory effects of heparin and drug delivery systems based on it on the molecular mechanisms of (multiple) drug resistance in (onco) pathological conditions of bone tissue, especially osteosarcoma.

摘要

现代医疗保健的主要问题之一是,无论是老年人群还是年轻人群,肿瘤疾病的数量都在不断增加。化疗作为癌症控制的主要方法,其效果不佳在很大程度上与肿瘤细胞中多药耐药性的出现有关。目前正在积极探索克服恶性细胞对药物耐药性的新解决方案。另一个严重问题是肿瘤细胞本身和抗肿瘤药物引起的免疫抑制。在这种情况下,肝素是一种属于糖胺聚糖类的生物分子,具有广泛的生物活性,包括免疫调节和抗肿瘤特性,因此备受关注。在专注于骨骼与免疫细胞协作的“骨免疫学”新领域快速发展的背景下,肝素及其基于它的递送系统对于恶性骨肿瘤的肿瘤治疗可能具有重要意义。骨肉瘤是一种罕见但高度侵袭性、对化疗耐药的恶性肿瘤,影响年轻成年人,其特点是不断复发和转移。本综述描述了肝素及其基于它的药物递送系统对骨组织(尤其是骨肉瘤)(肿瘤)病理状况下(多重)耐药性分子机制的直接和免疫介导的调节作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6bf/9612132/429c8b037972/pharmaceutics-14-02181-g001.jpg

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