School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, PR China.
School of Chemical Engineering, Pusan National University, Busan 46241, Republic of Korea.
J Control Release. 2022 Sep;349:963-982. doi: 10.1016/j.jconrel.2022.08.005. Epub 2022 Aug 10.
Stimuli-responsive drug delivery systems based on polymeric nanovehicles are among the most promising treatment regimens for malignant cancers. Such intelligent systems that release payloads in response to the physiological characteristics of tumor sites have several advantages over conventional drug carriers, offering, in particular, enhanced therapeutic effects and decreased toxicity. The tumor microenvironment (TME) is acidic, suggesting the potential of pH-responsive nanovehicles for enhancing treatment specificity and efficacy. The synthetic polypeptide poly(l-histidine) (PLH) is an appropriate candidate for the preparation of pH-responsive nanovehicles because the pK of PLH (approximately 6.0) is close to the pH of the acidic TME. In addition, the pendent imidazole rings of PLH yield pH-dependent hydrophobic-to-hydrophilic phase transitions in the acidic TME, triggering the destabilization of nanovehicles and the subsequent release of encapsulated chemotherapeutic agents. Herein, we highlight the state-of-the-art design and construction of pH-responsive nanovehicles based on PLH and discuss the future challenges and perspectives of this fascinating biomaterial for targeted cancer treatment and "benchtop-to-clinic" translation.
基于聚合纳米载体的刺激响应型药物递送系统是恶性癌症最有前途的治疗方案之一。与传统药物载体相比，这种针对肿瘤部位生理特征释放有效载荷的智能系统具有多种优势，特别是增强了治疗效果和降低了毒性。肿瘤微环境 (TME) 呈酸性，这表明 pH 响应型纳米载体具有增强治疗特异性和疗效的潜力。合成多肽聚（L-组氨酸）（PLH）是制备 pH 响应型纳米载体的合适候选物，因为 PLH 的 pK（约 6.0）接近酸性 TME 的 pH 值。此外，PLH 上的侧链咪唑环在酸性 TME 中产生 pH 依赖性的疏水性-亲水性相转变，触发纳米载体的失稳和随后封装的化疗药物的释放。在此，我们重点介绍基于 PLH 的 pH 响应型纳米载体的最新设计和构建，并讨论这种有吸引力的生物材料在靶向癌症治疗和“从实验室到临床”转化方面的未来挑战和前景。
