National Science Review: Breakthroughs . . The new strategy proposed by Liu Hongke/Zhao Jin/Guo Zijian has successfully achieved targeted anticancer drugs manufactured in tumors

Liu Hongke of Nanjing Normal University and Zhao Jin and Guo Zijian of Nanjing University jointly published a research paper entitled "Using bioorthogonally catalyzed fatality strategy to generate mitochondria-targeting antitumor metallodrugs in vitro and in vivo" online by simulating synthetic deaths The characteristics of the selection of ru-N3 and chemically modified large yellow acid rhein-alkyne, which are not toxic to tumors and normal cells, were selected as precomms, and the copper ion concentration of tumor cells/lotus mice was much higher than that of normal cells, and highly active tumor-targeted drug Ru-rheinein was obtained through a fast and efficient orthosis reaction.
controlled experiments showed that the above-mentioned biological ortho reactions did not occur in normal cells and therefore did not produce toxicity.
ru-rhein targets the mitochondrials of tumor cells (greater than 80%), causing tumor death through autophagy.
, a new method based on inductively coupled plasma mass spectrometography (ICP-MS) was established to determine the yield of cell reaction products.
experiments show that the strategy of "bio orthosis catalytic death" is universal.
In summary, the strategy of using tumor cells and living organisms as an anti-cancer drug manufacturing plant not only avoids the decomposition and inferction of the drug during transport and storage, but also reduces the toxic side effects caused by the drug's interaction with bioactive molecules when it enters the body.
strategy of "bio orthotic catalytic death" provides a new approach and platform for drug development for precise and efficient treatment of diseases.
cancer is one of the most serious diseases that threaten human life and health, and the development of anti-cancer drugs is directly related to human life and health.
the current clinical use of anti-tumor drugs have low efficiency, poor selectivity, toxic side effects and drug resistance and other shortcomings.
to selectively kill cancer cells but minimize side effects on normal cells has been a major challenge in drug research.
synthetic lethality was proposed by geneticists nearly a century ago and has recently been used to develop precise anti-cancer treatments.
In order to use the concept of synthetic lethality in the design of chemical anticancer drugs, the study developed a bio orthosis catalytic lethality (BCL) strategy to produce targeted anti-tumor metal drugs both in vitro and in vivo.
through a unique endo-copper catalytic laminated nitride olefin ring addition (CuAAC) reaction, no external copper catalyst is required to produce metal jaundols from two non-toxic Ru-N3 and large yellow acid olefin hydrocarbons.
the study designed the non-toxic Ru-arene/Ru-N3 and jaundial olefin hydrocarbons to perform this strategy, with high production of mitochondrial-targeted product Ru-rhein (-gt; 83%) and high anti-tumor properties in-body.
BCL strategy has a significant anti-cancer effect on the mouse model of lotus tumor.
Interestingly, the combination of metal-aromatic hydrocarbon complexes and jaundial acid can convert two non-toxic substances into targeted anti-cancer metal drugs in vitro and in vivo through CuAAC reactions, while the product, jaundate, is non-toxic to normal cells.
study explains the anti-cancer agent of jaundice and induces autophagy by increasing the damage of reactive oxygen and mitochondrials.
study explores the generality of BCL strategies and extends them to other metallic ensegings, such as Os-aromatics and Ir-aromatic hydrocarbons.
compared to traditional cancer treatments, this work proposes a new method for producing targeted metal drugs from non-toxic objects in metal-based chemotherapy through BCL strategies.
Liu Hongke of Nanjing Normal University (first completed unit), Professor Zhao Jin of Nanjing University and fellow Guo Zijian are co-authors of the newsletter.
first author of this thesis is Dr. Xue Xuling, a postdoctoral student at Nanjing Normal University.
Chenggen, a professor at the School of Pharmacy at the Chinese University of Pharmacy, also contributed to the study.
the study was funded by the National Natural Science Foundation of China.
。