Zhu Ying, Wang Liying, Li Yiping, Huang Zhewei, Luo Shiyao, He Yue, Han Han, Raza Faisal, Wu Jun, Ge Liang
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Xiang, Nanjing, 210009, China.
Biomater Sci. 2020 Oct 7;8(19):5415-5426. doi: 10.1039/d0bm01004a. Epub 2020 Sep 2.
Traditional anti-tumor drugs still have some shortcomings, such as low solubility, poor selectivity and poor bioavailability, which decrease their anti-tumor efficacy and aggravate systemic toxicity and side effects. In this paper, pH/redox dual responsive IC1-R peptide hydrogels were designed as drug delivery materials for the anti-tumor drug paclitaxel (PTX). The physical and chemical properties of drug-loaded IC1-R peptide hydrogels were characterized by pH/redox sensitivity, drug release, physical description, encapsulation rate, circular dichroism, electron transmission microscopy, and rheological tests. In vitro cytotoxicity and in vivo efficacy were studied to evaluate the anti-tumor efficacy of the PTX-loaded hydrogel. IC1-R was found to have high sensitivity to pH/redox conditions, and the encapsulation rate can reach more than 98% at different PTX dosages. The structure of the IC1-R peptide was found to be a β-sheet under neutral conditions, which met the requirement for nanofiber network formation. Transmission electron microscopy and rheology tests confirmed that the suitable meshwork structure and improved mechanical and injectable properties of this hydrogel. In vitro and in vivo results showed that the blank hydrogel had good biological safety and confirmed the pH/redox sensitive properties of IC1-R-PTX, which allowed sustained delivery of the drug and enhanced tumor inhibition. In conclusion, this kind of PTX-loaded peptide hydrogel, which was formed in vitro, can be injected into tumors and can continuously and slowly release anti-tumor drugs under the stimulation of the tumor microenvironment to achieve the best anti-tumor effect and reduce toxicity and side effects. This biofunctional material has broad prospects in the field of drug delivery.
传统抗肿瘤药物仍存在一些缺点，如溶解度低、选择性差和生物利用度低，这降低了它们的抗肿瘤疗效，并加重了全身毒性和副作用。本文设计了pH/氧化还原双响应IC1-R肽水凝胶作为抗肿瘤药物紫杉醇（PTX）的药物递送材料。通过pH/氧化还原敏感性、药物释放、物理描述、包封率、圆二色性、电子透射显微镜和流变学测试对载药IC1-R肽水凝胶的物理和化学性质进行了表征。研究了体外细胞毒性和体内疗效，以评估载PTX水凝胶的抗肿瘤疗效。发现IC1-R对pH/氧化还原条件具有高敏感性，在不同PTX剂量下包封率可达98%以上。发现IC1-R肽在中性条件下的结构为β-折叠，满足纳米纤维网络形成的要求。透射电子显微镜和流变学测试证实了该水凝胶具有合适的网状结构以及改善的机械性能和可注射性。体外和体内结果表明，空白水凝胶具有良好的生物安全性，并证实了IC1-R-PTX的pH/氧化还原敏感特性，这使得药物能够持续递送并增强肿瘤抑制作用。总之，这种体外形成的载PTX肽水凝胶可注射到肿瘤中，并能在肿瘤微环境的刺激下持续缓慢释放抗肿瘤药物，以达到最佳抗肿瘤效果并降低毒性和副作用。这种生物功能材料在药物递送领域具有广阔的前景。
