硼酸酯键在药物传递体系中的应用

doi:10.6023/cjoc202006060

摘要/Abstract

刺激响应性药物载体由于其优异的控释性能, 在生物医药领域引发了广泛的关注并得到了极为快速的发展. 硼酸酯键因构筑条件简单、生物相容性好以及能够响应生物体内pH、葡萄糖、三磷酸腺苷(ATP)等多种微环境变化的优势被广泛用于刺激响应性药物载体的构筑. 基于硼酸酯键的药物载体类型有药物-聚合物偶联、聚合物胶束、线性-超支化聚合物和介孔二氧化硅等, 它们既能负载抗癌药物, 又能递送胰岛素和基因. 药物通过共价或非共价作用负载到载体上, 并利用硼酸酯键在不同环境下的形成与断裂实现药物的可控释放. 从药物类型、载体类型、药物与载体的结合方式以及硼酸酯键的断裂机制四个方面综述了硼酸酯键在药物传递体系中的应用, 并对其当前面临的主要挑战和未来的发展趋势进行了总结和展望.

关键词: 刺激响应, 药物载体, 硼酸酯键

Because of its excellent controlled release properties, stimulus-responsive drug carriers have attracted extensive attention in the field of biomedicine and have achieved extremely rapid development. Boronate bonds have been widely used as a stimulus-responsive site in the construction of drug carriers because of its simple construction conditions, good biocompatibility, and fast responsiveness to various micro-environmental changes such as pH, glucose and 5'-adenosine triphosphate (ATP) concentration in vivo. The types of drug carriers based on boronate bonds include drug-polymer conjugate, polymer micelles, linear-hyperbranched polymers and mesoporous silica, which could load anticancer drugs and deliver insulin and genes. Besides, drugs could be integrated into carrier by covalent bonding, physical encapsulation, and electrostatic interactions, which could be released at specific sites via endogenous stimuli. The application of boronate bond in drug delivery system is reviewed from four aspects: drug types, carrier types, combination mode of drug and carrier as well as breaking mechanism of boronate bond. The main challenges and future advances in this field are also detailed.

Key words: stimulus-responsive, drug carrier, boronate bond

引用此文

王李娟, 盛显良, 王杰, 张玉辉. 硼酸酯键在药物传递体系中的应用[J]. 有机化学, 2021, 41(2): 567-581.

Lijuan Wang, Xianliang Sheng, Jie Wang, Yuhui Zhang. Application of Boronate Bond in Drug Delivery System[J]. Chinese Journal of Organic Chemistry, 2021, 41(2): 567-581.

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图/表 13

图1. Dex/Chol-PBA纳米组装体的形成过程及其用于溶酶体酸度靶向的pH响应的药物递送示意图

Figure 1. Schematic illustration of the formation process of Dex/Chol-PBA nanoassembly and its pH-responsive drug delivery for lysosomal acidity targeting

图2. DOX/BNPs纳米组装体的形成过程示意图

Figure 2. Schematic illustration of the formation process of DOX/BNPs nanoassembly

图3. PMAPBA/Dextran纳米组装体形成过程的示意图

Figure 3. Schematic illustration of the formation process of PMAPBA/Dextran nanoassembly

图4. 基于WP5?G超两亲物的超分子囊泡的形成过程及其葡萄糖响应的胰岛素递送示意图[28]

Figure 4. Schematic illustration of the formation process of supramolecular vesicles based on WP5?G supra-amphiphile and their glucose-responsive insulin delivery[28]

图5. 主体-客体复合物WP5?G的超分子囊泡形成过程及其在高糖状态下的胰岛素和GOx递送示意图[29]

Figure 5. Schematic illustration of the formation process of supramolecular vesicles of the host-guest complex WP5?G as well as their insulin and GOx delivery under hyperglycemic state[29]

图6. pPBA-AND纳米组装体的形成和裂解示意图

Figure 6. Schematic illustration for the formation and destruction of pPBA-AND nanoassembly

图7. HAGlu-BTZ多糖偶联物的构筑示意图[40]

Figure 7. Schematic illustration for the construction of HAGlu-BTZ polysaccharide conjugates

图8. 硼酸盐交联胶束(BCM)的形成过程及其响应于甘露醇和/或酸性pH值的疏水染料或药物递送示意图[42]

Figure 8. Schematic illustration of the formation process of the boronate crosslinked micelles (BCM) and its hydrophobic dye or drug delivery in response to mannitol and/or acidic pH values

图9. 动态稳定的mPEG-PBA/HEHDO纳米结构的形成过程示意图

Figure 9. Schematic illustration of the formation process of dynamically stable mPEG-PBA/HEHDO nanoconstruction

图10. 交联MSN-PAA-AGA的制备及其双重响应药物释放过程的示意图[53]

Figure 10. Schematic illustration of the preparation of cross-linked MSN-PAA-AGA and its dual-responsive drug release process

图11. Si-Dox@HA纳米结构的制备及其用于H2O2响应的Dox释放过程示意图[55]

Figure 11. Schematic illustration of preparation of Si-Dox@HA nanoconstruction and its H2O2-responsive Dox release process

图12. 装载ETO的CCLMs的形成过程及其用于pH和氧化还原响应的ETO递送示意图[58]

Figure 12. Schematic illustration of formation process of ETO-loaded CCLMs and its pH- and Redox-responsive ETO delivery

图13. 基于α-CD和PBEM的主客体复合物的形成及其用于双重刺激响应的药物释放过程示意图

Figure 13. Schematic illustration of formation of host-guest complexation between α-CD and PBEM as well as its dual stimuli-responsive drug release process

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