Construction Of Nanozyme-metal Organic Framework Composites And Its Application In Tumor Theranostic

Tumors are divided into benign tumors and malignant tumors.Malignant tumors have become the primary threat to human health because of their fast growth and strong metastasis.According to the world’s latest global cancer burden data in 2020,there will be 19.29 million new cancer cases and 9.96 million cancer deaths in 2020 alone,which is equivalent to 20 people losing their precious lives due to cancer in one minute.Traditional cancer treatment methods include chemotherapy,surgery and radiotherapy.Although these methods can achieve the purpose of treatment to a certain extent,patients have to bear great pain and side effects brought by traditional treatment,which seriously affects the normal quality of life of patients.Therefore,it is urgent to develop a series of new treatment methods to achieve effective treatment of tumor and reduce the pain of patients.In recent years,more and more researchers began to explore the possibility of combining nanoparticles with tumor therapy,and new therapeutic methods such as chemodynamic therapy（CDT）,photothermal therapy（PTT）,photodynamic therapy（PDT）and immunotherapy were born.However,due to the complexity of tumor microenvironment,a single treatment method cannot achieve the goal of completely inhibiting tumor growth,which urges researchers to improve or regulate the tumor microenvironment and develop a variety of treatment methods to improve the anti-tumor ability of nanoparticles.In this paper,we mainly designed and synthesized nanozyme-metal organic framework composites,obtained two new therapeutic platforms for tumor treatment by using their inherent enzyme activity and material characteristics.The details of this paper were as follows:1.The ultrafine nanozyme-metal organic framework composite（Cu-Pd@MIL-101）was synthesized by galvanic replacement reaction.Because the complex has excellent peroxidase-like（POD-like）activity,superoxide dismutase-like（SOD-like）activity and glutathione（GSH）consumption ability in tumor microenvironment,the purpose of enhanced CDT is realized.Both in vitro and in vivo results show that Cu-Pd@MIL-101 has good biosafety and biocompatibility,and can inhibit the growth of tumor without causing damage to normal cells and tissues.This is mainly because the enzyme activity of the Cu-Pd@MIL-101 can only be released under specific conditions,realizing the selective tumor killing effect.2.ZIF-8（Pd Cu Au）@Mn O₂ composite was synthesized by a simple method,and its surface modified m DSPE-PEG made the material have good biocompatibility.Because the tumor cells are rich in glutathione（GSH）,they can react with Mn O₂ to produce Mn²⁺for magnetic resonance imaging（MRI）contrast agent,and ZIF-8（Pd Cu Au）@Mn O₂ has strong POD-like activity,which can catalyze the decomposition of H₂O₂in the tumor microenvironment into hydroxyl radical（·OH）to achieve the purpose of CDT.At the same time,the complex has strong absorption in the NIRⅡ,and can also achieve the NIRⅡphotothermal therapy treatment and photothermal enhancement CDT.In vivo and in vitro experiments confirmed that ZIF-8（Pd Cu Au）@Mn O₂ can be used as a GSH-responsive MRI guided PTT-CDT synergetic therapy agent.