In Situ Prodrug Activation by an Affibody-Ruthenium Catalyst Hybrid for HER2-Targeted Chemotherapy.
Zhennan ZhaoXuan TaoYanxuan XieQi LaiWenkai LinKai LuJinhui WangWei XiaZong-Wan MaoPublished in: Angewandte Chemie (International ed. in English) (2022)
Transition-metal catalysts exhibit great potential as therapeutic agents to inhibit tumor growth. However, the precise delivery and in situ catalysis are challenging in catalytic medicine. Herein, we report an anti-HER2 affibody-ruthenium catalyst hybrid, named Ru-HER2 for selective and effective killing of cancer cells. Ru-HER2 binds to the HER2 receptor on a tumor cell and in situ catalyzes the activation of gemcitabine prodrug, resulting in enhanced selectivity in suppression of tumor growth and reduction of side effects. Immunoblotting reveals that Ru-HER2 in combination with gemcitabine prodrug can not only induce DNA damage, but also effectively block the HER2 signaling pathway in cancer cells. Therefore, the HER2-targeted chemotherapy exhibits substantially high anticancer activity toward HER2-positive cancer cells in vitro and in vivo. In a word, we report the first affibody-ruthenium catalyst hybrid and reveal its potential for effective HER2-targeted cancer chemotherapy.
Keyphrases
- cancer therapy
- locally advanced
- transition metal
- highly efficient
- dna damage
- drug delivery
- room temperature
- ionic liquid
- metal organic framework
- signaling pathway
- rectal cancer
- visible light
- reduced graphene oxide
- single cell
- carbon dioxide
- squamous cell carcinoma
- radiation therapy
- energy transfer
- drug release
- papillary thyroid
- genome wide
- epithelial mesenchymal transition
- dna repair
- young adults
- pi k akt
- cell therapy
- climate change
- childhood cancer