State Key Laboratory of Natural Medicines and Department of Pharmaceutics, China Pharmaceutical University, No. 24 Tongjia Xiang, Nanjing, 210009, Jiangsu, China.
Biomater Sci. 2019 Apr 23;7(5):2023-2036. doi: 10.1039/c9bm00139e.
Intratumoral delivery of chemotherapeutic agents may permit the localization of drugs in tumors, decrease nonspecific targeting and increase efficacy. The pH-responsive peptide hydrogel is considered a suitable carrier for chemotherapeutics via intratumoral injection. Thus, a study was carried out to develop a paclitaxel (PTX) drug delivery system using a pH-responsive FER-8 peptide hydrogel for tumor targeting. The pH-sensitive hydrogel system was characterized for loading capacity, acid sensitivity, structure, rheology, morphology, drug release, in vitro cytotoxicity and in vivo efficacy in H22 tumor-bearing mice. The stable FER-8 peptide hydrogel with high drug-loading capacity was formed at pH 7.4 by the self-assembly of peptide, whereas higher degradation was observed at an acidic pH. Circular dichroism and rheology confirmed the suitable meshwork structure and enhanced mechanical properties of the hydrogel. The FER-8 peptide hydrogel fibers were found to have an average size less than 500 nm at pH 7.4, which was confirmed by TEM and DLS analysis. Sustained release of PTX at pH 5.5 was observed for the FER-8 peptide hydrogel (HG-PTX) for almost 1 week. In vitro cytotoxicity studies indicated that the FER-8 peptide hydrogel increased the drug accumulation in HepG2 cells and effectively inhibited the growth of HepG2 tumor cells compared with free drugs. Furthermore, in vivo studies using H22-bearing mice indicated that the paclitaxel-loaded FER-8 peptide hydrogel significantly increased the amount of drugs in tumor tissues and showed prolonged retention (96 hours) at the tumor site by intratumoral injection. The in vivo anti-tumor studies confirmed the pH-sensitive properties of HG-PTX, which allowed the drug to be triggered by the acidic pH environment at tumor sites, provided sustained delivery of the drug and enhanced tumor inhibition. In conclusion, HG-PTX provides an attractive strategy and potential vehicle for efficient anti-cancer drug delivery. The carrier can enhance tumor targeting, prolong retention, reduce systemic side effects and increase the accumulation of drugs at the tumor site.
瘤内递送化疗药物可以使药物在肿瘤中定位，减少非特异性靶向并提高疗效。pH 响应性肽水凝胶被认为是通过瘤内注射递送化疗药物的合适载体。因此，进行了一项研究，以开发一种使用 pH 响应型 FER-8 肽水凝胶进行肿瘤靶向的紫杉醇（PTX）药物递送系统。对 pH 敏感的水凝胶系统进行了载药量、酸敏感性、结构、流变学、形态、药物释放、体外细胞毒性和荷 H22 肿瘤小鼠体内疗效的表征。在 pH 7.4 下，通过肽的自组装形成具有高载药量的稳定 FER-8 肽水凝胶，而在酸性 pH 下观察到更高的降解。圆二色性和流变学证实了水凝胶合适的网格结构和增强的机械性能。在 pH 7.4 下，FER-8 肽水凝胶纤维的平均尺寸小于 500nm，这通过 TEM 和 DLS 分析得到了证实。在 pH 5.5 下，观察到 FER-8 肽水凝胶（HG-PTX）中 PTX 的持续释放将近 1 周。体外细胞毒性研究表明，与游离药物相比，FER-8 肽水凝胶增加了 HepG2 细胞中的药物积累，并有效抑制了 HepG2 肿瘤细胞的生长。此外，使用荷 H22 小鼠的体内研究表明，载紫杉醇的 FER-8 肽水凝胶通过瘤内注射显著增加了肿瘤组织中的药物含量，并在肿瘤部位表现出延长的保留（96 小时）。体内抗肿瘤研究证实了 HG-PTX 的 pH 敏感性，这使得药物能够被肿瘤部位的酸性 pH 环境触发，提供药物的持续释放，并增强肿瘤抑制。总之，HG-PTX 为高效抗癌药物递送提供了一种有吸引力的策略和潜在的载体。该载体可以增强肿瘤靶向性、延长保留时间、减少全身副作用并增加药物在肿瘤部位的积累。
