The latest research results of Professor Zhu Limin's research group and collaborators in the field of degradable nano diagnosis and treatment integration

Recently, Professor Zhu Limin's research group of Donghua University has made new progress in the field of integrated diagnosis and treatment of cancer The relevant research results are as follows: a multifunctional biodegradable nanocomposite for cancer therapeutics, DOI: 10.1002/advs.201802001) was published online in advanced science, an international well-known academic journal Wu Jianrong, Ph.D student of School of chemistry, chemical engineering and Bioengineering, is the first author of the thesis Professor Zhu Limin and Dr Tang Ranran, Nanjing Maternal and child health care institute affiliated to Nanjing Medical University, are the co correspondents The integration of nano diagnosis and treatment is one of the main research directions of personalized tumor treatment Through the rational design and synthesis of nano materials, the current clinical diagnosis and treatment of two separate processes and functions are integrated into a nano carrier, forming a nano platform for the integration of diagnosis and treatment It can diagnose the disease in real time, accurately and treat simultaneously It can monitor the curative effect and adjust the dosage plan at any time in the treatment process, which is conducive to achieve the best treatment effect and reduce the toxic and side effects Nano carrier system has good modifiability and loading activity (or function) species ability, which is very conducive to building an integrated platform for nano diagnosis and treatment, and has great application value in the field of precision medicine In recent years, the diagnosis and treatment system based on mesoporous silica nanoparticles has become a research hotspot of many researchers, because they show good biocompatibility, response control release, tumor targeting and other functions Therefore, silica based nano diagnosis and treatment system has great potential in the field of nano biomedicine However, the uncontrolled degradation of silica skeleton and long-term retention in vivo will lead to serious and unpredictable potential risks, which seriously limits its clinical application Therefore, the key to solve the problem is to achieve the responsive degradation of silica skeleton In view of these bottlenecks, Wu Jianrong, a doctoral student of the research group, has developed a variety of new multi-functional tumor diagnosis and treatment integrated platforms based on mesoporous organic silicon oxide in recent years, and achieved a series of high-level research results The research work was published in the international famous journals such as ACS appl Mater Interfaces (2018, 10, 42115), Chemical Engineering Journal (chem Eng J 2018, 342, 90) and J Biomed Nanotechnol (DOI: 10.1166 / JBN 2019.2729) In this paper, the research team synthesized small size organic-inorganic hybrid hollow mesoporous organosilicon nanocapsules (hmons) doped with disulfide bond according to the mechanism of "chemical homology" Using the huge cavity of hmons, they loaded perfluoropentane (PFP) and near-infrared dye (ICG) simultaneously to obtain a biodegradable mesoporous nano diagnostic and therapeutic agent (ICG / PFP @ hmop-peg), which was used in the photoacoustic / ultrasound multimodal imaging-mediated chemotherapy photothermal synergistic treatment of tumor The highlight of this work lies in the use of paclitaxel as a pore sealing agent for organosilicon Once the therapeutic agents enter the tumor cells through passive targeting, the disulfide bond in paclitaxel prodrug and its skeleton will be opened by high concentration of GSH, triggering the biodegradation of nanosystem Under the action of near-infrared light, the near-infrared light energy can be transformed into heat energy by loading the near-infrared dye ICG, which realizes the synergistic effect of heat and chemotherapy At the same time, the liquid-gas phase transition of PFP produces bubbles, which further form micro bubbles to realize ultrasonic imaging The nano therapeutic agent designed in this work consists of organic silica bridged by disulfide bond and paclitaxel pre drug pore sealer with reductive response The introduction of disulfide bond into silica skeleton can not only keep its high stability under physiological conditions, but also realize the responsive degradation under reductive conditions, which is conducive to the removal from the body to the body It is worth mentioning that the long-term toxicity of nanoparticles can be alleviated by their bioresponsive degradation behavior, which will be helpful for the future application in clinical experiments At the same time, the strategy of self sealing of chemotherapeutic drugs effectively avoids the unpredictable toxicity of other sealing agents The strategy of paclitaxel pre drug pore sealing proposed in this paper provides a new idea for the design and performance improvement of nano diagnosis and treatment platform based on mesoporous silicon, and realizes its wide application in clinical diagnosis and treatment The researchers believe that this research will open a window for biomedical applications based on silicone nano agents and provide new ideas for tumor ultrasound imaging The research work was supported by NSFC, Shanghai Science and Technology Commission and other projects Professor Zhu Limin's research group has been engaged in the design and application of biomedical nanomaterials for many years These include the design of chitosan based tumor targeting smart drug loaded nanomaterials (chem Eng J 2019, 369, 134-149; drug deliv, 2018, 25, 1275-1288; colludes and surfaces a 2018, 564, 122-130), and the construction of two-dimensional nano tablet drug loaded systems (colludes and surfaces B 2019, 173, 101 – 108; J colludes Interf SCI 2019, 539, 433 – 441) and the design of biomimetic encapsulation responsive nano carriers of platelet membrane (int J Pharmaceut 2019, 559, 289-298; J nanobiotechnol 2019, 17, 60).