Nano Today: A new strategy for the catalytic treatment of tumors by nanoenzyme pre-drug drugs.

Recently, Nano Today published online a research paper by the Institute of Biophysics of the Chinese Academy of Sciences/Chinese Academy of Sciences Nanoenzyme Engineering Laboratory, 'A Metal-Free Nanozyme-Activated Prodrug Strategy for Targeted Tumor Catalytic Therapy'.
this work for the first time put forward a new strategy for the use of nanoenzyme pre-drug system for tumor catalytic treatment, which provides new ideas for tumor therapy and further expands the biomedical application of nanoenzyme.
enzymatic therapy has always been a very attractive disease treatment strategy because enzyme catalysis is highly efficient and specific.
e.g. enzyme-activated pre-drug therapy strategy, because of its high selectivity and low toxicity, is a promising anti-cancer strategy, especially spicy root peroxidase (HRP) and pre-drug pyridoxine-3-acetic acid (IAA) has been proven to be an effective preenzyme system.
the system is applied in vivo, HRP can be introduced into tumor cells by antibody association or gene delivery.
drug IAA is a system after drug delivery, through free diffusion to the tumor site, and then react with HLP to release the active ingredient methyl pyridine free agent, killing tumor cells.
However, there are two major defects in this strategy: First, antibody even targeting is faced with the limitation of protease degradation and HRP's function outside tumor cells, thus limiting its tumor killing effect, and at the same time, in gene delivery, effective tumor target delivery and selective expression of exogenetic HRP in tumor cells are difficult, and there are also problems of genetically modified safety.
second, because the pre-drug IAA is reached to the tumor site through free diffusion, it is insufficiently collected at the tumor site to trigger enough catalytic reaction to kill the tumor.
, to improve the therapeutic effect of the enzyme activation pre-drug strategy, it is necessary for the enzyme to reach the tumor site efficiently, and to improve the ex-drug's abunding at the tumor site.
to solve these problems, the researchers proposed a pre-drug strategy for the activation of enzymes based on nanoenzymes.
nanoenzyme is a nanomaterial with steroid catalytic activity discovered in recent years, and is a new generation of analog enzymes.
Compared with natural enzymes, nanoenzymes are highly stable and do not degrade by proteases, and nanoenzymes are versatile as nanomaterials that, in addition to enzyme catalysis activity, can also be loaded with drugs or targeted molecules as nano carriers, so it is expected to develop more efficient enzyme catalytic therapy strategies.
nanoenzymes are mainly inorganic nanomaterials, and their activity is mainly redox enzyme activity.
Most of the nanoenzymes currently reported are metal oxides (e.g. iron oxide, copper oxide, zircoxide, etc.) or precious metals (gold, silver, palladium, platinum, etc.), which are difficult to degrade metabolism when used in the body, and may release metal ions to produce cytotoxicity, so there are potential biocompatibility and safety issues.
In recent years, carbon nanoenzymes have received widespread attention, such as graphene, carbon nanotubes, carbon dots, etc., especially isomer doping may better simulate the catalytic activity center structure of natural enzymes, showing high peroxidase activity;
based on the peroxidase activity of carbon nanoenzymes to establish nanoenzyme pre-drug treatment strategies for tumors.
, the biosecurity and stability of non-metallic elements doped with carbon nanoenzyme to improve its peroxidase activity.
the researchers simulated the peroxidase activity of a series of carbon nanoenzymes doped with non-metallic elements using theoretical calculations, and found that N and P double doped nanoenzymes had the lowest reaction speed and therefore the highest enzyme activity.
, the synergy of N and P increased the peroxidase activity of carbon nanoenzyme by nearly 3 times, which is consistent with the theoretical calculation and prediction.
results also show that for carbon nanoenzymes, in addition to doping metals, optimizing non-metallic structures can significantly improve the activity of nanoenzymes.
, the researchers built a tumor-targeted nanoenzyme pre-drug system.
nanoenzyme pre-drug system has also shown good anti-tumor effect and biological safety in animal experiments.
The results show that it is feasible to replace natural enzymes with nanoenzymes for the treatment of tumors with enzyme-activated pre-drugs, while nanoenzymes as vectors can deliver pre-drugs to tumor sites more efficiently, giving full play to the dual functions of enzyme catalysis and nano-carriers.
, this study provides a new strategy for the treatment of pre-enzymatic tumors and is expected to become a new direction of targeted catalytic therapy of tumors.
work was carried out in collaboration with the Institute of Biophysics of the Chinese Academy of Sciences, Yangzhou University and Jiangxi Normal University.
The Institute of Biophysics of the Chinese Academy of Sciences/Chinese Academy of Nanoenzyme Engineering Laboratory, Dr. Yan Xiyun, Researcher Gao Lisheng and Researcher Fan Kelong are co-authors, and The Ph.D. students of the Institute of Biophysics of the Chinese Academy of Sciences, Liang Wei, Associate Professor Yu Juqun of Yangzhou University and Dr. Gao Xuexuan of Jiangxi Normal University are co-authors.
research has been funded by the National Natural Science Foundation of China, the National Key Research and Development Program, the Leading Special Project of the Chinese Academy of Sciences, and the Youth Innovation Promotion Association of the Chinese Academy of Sciences.
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