Intelligent drugs based on notch protein remodeling: a defensive targeting strategy for tumor therapy

• Published in: Cell death & disease 2024-08, Vol.15 (8), p.632-13, Article 632
• Main Authors: Sun, Yuliang, Lu, Yilin, Li, Xinze, He, Yanan, Yong, Then Kong, Keng, Cheong Soon, Yahaya, Badrul, Liu, Yanli, Lin, Juntang
• Format: Article
• Language: English
• Subjects: 13/100; 13/31; 13/95; 631/154/152; 631/67/1059/602; Animals; Antibodies; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biochemistry; Biomedical and Life Sciences; Cancer therapies; Cell Biology; Cell Culture; Cell Line, Tumor; Drug delivery; Drugs; Endostatin; ErbB-2 protein; Humans; Immunology; Life Sciences; Mesenchymal stem cells; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Mice; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Notch protein; Receptors, Notch - metabolism; Toxicity; Tumor cells
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-024-07008-7

In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple “wisdom” by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSC Endostatin ). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.