Gorzkiewicz Michał, Klajnert-Maculewicz Barbara
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland.
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland; Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Strasse 6, 01069 Dresden, Germany.
Eur J Pharm Biopharm. 2017 May;114:43-56. doi: 10.1016/j.ejpb.2016.12.030. Epub 2017 Jan 13.
Dendrimers constitute a class of hyperbranched macromolecules with several potential applications due to their unique properties such as a well-defined structure, multivalency and biocompatibility. These polymers became one of the most promising drug nanocarriers, providing improved solubility of therapeutics, high loading capacity and controllable biodistribution pattern. In addition, the use of dendrimers as drug delivery devices in cancer therapies may help to overcome the resistance mechanisms by transporting activated drug molecules directly to cancer cells. In the recent years, dendrimers were intensively studied for delivery of nucleoside analogues (NAs), essential elements of antiviral therapies, as well as treatments of leukemia, lymphoma and various types of solid tumors. These agents act as antimetabolites, competing with physiological nucleosides, and interacting with intracellular enzymes and nuclear acids to induce cytotoxicity. However, efficiency of NAs-based therapies is often limited by factors like fast metabolism, disadvantageous biodistribution, low solubility and various side effects. In case of treatment of leukemia, target cells usually develop drug resistance, which reduces the activity of nucleoside analogues even further. Thus, drug carrier systems are studied to improve the efficacy and specificity of action of these compounds. In this review, we summarize available data concerning the possibility of application of dendrimers as delivery devices for nucleoside analogues and their active, triphosphate forms.
树枝状大分子是一类超支化大分子，由于其具有明确的结构、多价性和生物相容性等独特性质，因而具有多种潜在应用。这些聚合物成为了最有前景的药物纳米载体之一，能提高治疗药物的溶解度、具有高载药量以及可控的生物分布模式。此外，在癌症治疗中使用树枝状大分子作为药物递送装置，可能有助于通过将活化的药物分子直接运输到癌细胞来克服耐药机制。近年来，树枝状大分子被广泛研究用于递送核苷类似物（NAs），这是抗病毒疗法的重要组成部分，同时也用于治疗白血病、淋巴瘤和各种实体瘤。这些药物作为抗代谢物，与生理性核苷竞争，并与细胞内酶和核酸相互作用以诱导细胞毒性。然而，基于核苷类似物的疗法的效率常常受到快速代谢、不利的生物分布、低溶解度和各种副作用等因素的限制。在白血病治疗中，靶细胞通常会产生耐药性，这进一步降低了核苷类似物的活性。因此，人们正在研究药物载体系统以提高这些化合物的疗效和作用特异性。在本综述中，我们总结了有关树枝状大分子作为核苷类似物及其活性三磷酸形式的递送装置的应用可能性的现有数据。
