基于苯甲酰亚胺的高分子药物载体与支架材料
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摘要
苯甲酰亚胺(Benzoic-imine)是近期被报道的少数能够响应由重大疾病引起的体内内源性pH改变的化学结构之一。由于苯环与碳氮双键共轭作用,使其在正常生理pH值(～7.4)稳定,在弱酸性pH值(<6.8)水解。基于苯甲酰亚胺基团的高分子输送体系,能够高效响应实体肿瘤、脑卒中半暗带等由病变组织内部无氧酵解导致的细胞外弱酸性环境,及因细胞内化所形成的内涵体、溶酶体等酸性环境,赋予该类载体被动靶向效应。另一方面,苯甲酰亚胺是一类重要的动态化学结构,由苯甲醛基团与氨基反应键合,反应条件温和。利用该反应能够在生理环境条件下构筑原位交联体系,获得具有注射能力的高分子水凝胶,用于生物活性物质输送或作为组织工程支架。亚胺形成与水解过程可逆,基于苯甲酰亚胺的生物医用体系不需永久改变材料化学结构,具有明确的代谢途径,为载体设计和材料选择提供方便。目前,苯甲酰亚胺结构已被用于制备环境响应性高分子组装体系、有机/无机杂化体系及高分子水凝胶。本文将介绍最近几年来基于苯甲酰亚胺基团的高分子药物输送体系和组织工程支架材料制备等方面的研究进展。
The benzoic-imine generated from amine and benzaldehyde groups is an interesting dynamic covalent bond. The bond is stable around neutral pH value(～7.4) arising from the existence of aromatic ring nest to the carbon-nitrogen double bond, while starts to hydrolyze at very mild acidic pH, e.g. the extracellular pH value of solid tumors(6.5～6.8). The hydrolysis kinetics can be tunable by the acidity of the environmental conditions, which becomes faster at endosome and lysosome pH values(ca. 4.5～6.5). These merits are promising to design and construct physiological pH responsive materials with tunable morphologies including polymeric aggregates, polymer/inorganic nanocomposites, microgels and bulk injectable hydrogels. Many potential applications have been demonstrated for delivery vehicles and/or scaffolds for tissue engineering. In this review, we summarizes the recent progresses in the design and synthesis of benzoic-imine dynamic bond contained polymeric systems for biomedical applications.
The benzoic-imine generated from amine and benzaldehyde groups is an interesting dynamic covalent bond. The bond is stable around neutral pH value(～7.4) arising from the existence of aromatic ring nest to the carbon-nitrogen double bond, while starts to hydrolyze at very mild acidic pH, e.g. the extracellular pH value of solid tumors(6.5～6.8). The hydrolysis kinetics can be tunable by the acidity of the environmental conditions, which becomes faster at endosome and lysosome pH values(ca. 4.5～6.5). These merits are promising to design and construct physiological pH responsive materials with tunable morphologies including polymeric aggregates, polymer/inorganic nanocomposites, microgels and bulk injectable hydrogels. Many potential applications have been demonstrated for delivery vehicles and/or scaffolds for tissue engineering. In this review, we summarizes the recent progresses in the design and synthesis of benzoic-imine dynamic bond contained polymeric systems for biomedical applications.
引文
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