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Abstract: pH-sensitive smart polymeric nanocarriers have been under development in the field of biomedicine due to permeabilization the physiological barriers readily to address the limitation of conventional chemotherapeutics delivery systems of low intracellular transport and targeting efficiency. Where traditional polymers kept stable under physiological neutral or acidic conditions, pH-sensitive polymeric nanocarriers underwent rapid degradation with a labile group in tumor acidic environment (around 5.0–6.0), allowing these biomaterials to achieve controlled drug release, drug pharmacokinetics improvement and antitumor biotherapeutic molecules efficiency enhancement compared with traditional polymers. This review mainly concentrated on properties of pH-sensitive polymers for biomedical purposes to construct the smart drug delivery system based on acid liable linkers which were categorized into pH-sensitive polymeric prodrugs composed of antitumor drugs (doxorubicin and paclitaxel) bounded to the polymer via acid liable linkers and pH-sensitive copolymeric nanocarriers prepared by block copolymers containing polymer blocks linked with acid-cleavable groups. Besides, advanced platforms in biomedicine for special biotherapeutic molecules delivery were reviewed in the article. Furthermore, several acid-sensitive linkages were reviewed to study the mechanism of the controlled pH-responsive drug delivery, such as hydrazone, acetal, cis-aconityl linker and β-thioether ester, as well as improvement of drug pharmacokinetics.

浙大一院赵青威、钦佳怡等 | 用于抗肿瘤药物靶向递送的pH敏感聚合物纳米载体

本综述论文聚焦用于抗肿瘤药物递送的pH敏感聚合物纳米载体。目前临床治疗中抗肿瘤药物存在毒副作用大、靶向性低的问题。针对肿瘤微环境设计的pH敏感聚合物材料可在体内正常生理条件下保持稳定状态，在肿瘤酸性环境（pH约5.0-6.0）中快速降解，实现药物的靶向性释放，从而提高疗效。此类pH敏感聚合物主要包括通过pH敏感键制备的药物大分子复合物及采用化学键合形成的嵌段共聚物用于包载药物，是一种极具潜力的药物靶向递送载体。本综述重点介绍pH敏感聚合物纳米载体组成及应用，系统阐释了聚合物纳米载体通过不同酸敏感键（腙、缩醛、β-硫醚酯等）实现pH敏感靶向性药物释放的机制以及药代动力学的研究。此外，本文进一步综述了特殊给药药物的靶向递送，拓宽了pH敏感聚合物材料在生物医药领域的应用。