肽
体内
化学
化疗
肿瘤微环境
癌症研究
甲氨蝶呤
内吞作用
药品
自愈水凝胶
癌症
癌细胞
细胞
药理学
生物物理学
生物化学
肿瘤细胞
医学
免疫学
内科学
生物
有机化学
生物技术
作者
Jiamin Zhang,Wenjing Lin,Lijun Yang,Aijie Zhang,Yumin Zhang,Jinjian Liu,Jianfeng Liu
出处
期刊:Biomaterials Science
[The Royal Society of Chemistry]
日期:2022-01-01
卷期号:10 (3): 854-862
被引量:38
摘要
Chemotherapy is the main treatment for cancer therapy. However, its anti-tumor efficiency is always impaired by the poor bioavailability and low tumor accumulation of chemotherapeutic drugs. The variation between the tumor microenvironment and normal tissue has been recognized as an effective tool to improve drug anti-tumor efficiency. Herein, we developed an injectable, pH-responsive, in situ self-assembled drug-peptide hydrogel (MTX-KKFKFEFEF(DA)) for highly efficient local tumor chemotherapy with few side effects. The small molecule drug, methotrexate (MTX), and pH-responsive linker, 2,3-dimethylmaleic anhydride (DA), were facilely conjugated onto the chain of the KKFKFEFEF peptide via an amidation reaction. The negatively charged drug-peptide (pH 7.4) can be activated to be positive and achieve a sol-gel phase transition under an acidic microenvironment (pH 6.5) both in vitro and in vivo, resulting in highly efficient cellular uptake and endocytosis capacities. Moreover, the in vivo anti-tumor therapeutic effect revealed that the MTX-KKFKFEFEF(DA) hydrogel exhibits long-term tumor retention time, much better tumor inhibition rate and negligible side effects after intratumoral injection into breast tumor-bearing mice. Therefore, this study reveals a versatile strategy for fabricating a pH-responsive drug-peptide hydrogel to improve the chemotherapeutic efficacy of drugs in cancer treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI