Recently, the research team (Mesoporous and low-dimensional nanomaterials research group) led by Researcher Chen Yu and Researcher Shi Jianlin of the Shanghai Institute of Ceramics, Chinese Academy of Sciences has carried out a variety of controlled synthesis of 2D MXene and biomedical applications for tumor diagnosis and treatment The systematic research work of MXene involves the enzymatic degradation of MXene itself, the phagocytic behavior of MXene in vitro and in vivo, the response to multi-region near-infrared light, efficient photothermal tumor therapy, diagnostic imaging, and biosafety evaluation of the system. Relevant research results were published in J. Am. Chem. Soc., Nano Lett. And Adv. Mater. The first author of the thesis was doctoral student Lin Han.

MAX phase ceramic bulk materials are transformed into Ti3C2 MXene nanosheets with ultra-thin two-dimensional structure through a two-step liquid phase etching and stripping process

Two-dimensional MXene is a new type of two-dimensional crystalline material that has attracted much attention. It includes a large number of transition metal carbides and nitrides, and has good electrical conductivity, hydrophilicity, and mechanical properties. The two-dimensional MXene phase nanosheet structure is mainly synthesized by liquid phase stripping. The main principle is to use the difference in force between different atomic layers in its precursor MAX material to achieve the A layer through a controlled etching process. Atom extraction, and then realize the stripping of MX layer (MXene). MXene generally exists in three forms: M2X, M3X2 and M4X3. MXene is used in energy storage and conversion, water purification, chemical sensing, light or electrocatalysis, and electrostatic shielding due to its rich physical and chemical properties, and is expected to make a breakthrough in the field of nanobiomedicine. On the one hand, the two-dimensional MXene with ultra-thin atomic layer thickness exhibits rich physical and chemical properties (including photothermal conversion performance, electron penetration, X-ray attenuation and surface plasmon resonance, etc.) and special biological effects (enzyme response degradation, Endocytosis, body distribution and metabolic dynamics, etc.). On the other hand, the precise controllable preparation of MXene elemental components and structural units within the sheet layer also provides a more extensive and flexible material science foundation for MXene‘s multifunctional exploration.

For the first time, the research team realized the peeling and acquisition of the near-monolayer structure of the small-sized two-dimensional MXene material (Ti3C2 MXene), and systematically studied the in vitro light-to-heat conversion performance, in vivo biosafety evaluation and in vivo photothermal treatment effect of MXene nanosheets (Nano Lett., 2017, 17, 384.). This work systematically illustrates the transformation of MAX phase bulk materials into nanosheets with ultra-thin two-dimensional structures through a two-step liquid phase etching and stripping process. The two-dimensional nanomaterials have good linear extinction in the near infrared (NIR) region Coefficient (25.2 Lg−1 cm−1) and excellent light-to-heat conversion efficiency (30.6%). After surface modification, Ti3C2-SP MXene showed good in vitro cell compatibility and in vivo biosafety, and achieved a significant effect of tumor photothermal ablation in the in vivo tail vein injection treatment mode. At the same time, in vivo Ti3C2 / The treatment model of PLGA implants also achieved the effect of ablation of xenografts in nude mice.

Subsequently, the research team further published an integrated diagnosis and treatment nano platform (Adv. Mater., 2018, 30, 1703284) based on the integration of two-dimensional Ta4C3 MXene nanosheets in vivo dual-mode PA / CT imaging and in vivo photothermal therapy. The ultra-thin layer structure of Ta4C3 MXene nanosheets and the CT signal of Ta element enhance the physical and chemical properties. Under the control of a controlled external field (near infrared light, X-ray), it can realize efficient in vivo photothermal conversion and in vivo PA / CT dual mode Imaging achieves the purpose of thermally ablating tumor cells without toxic and side effects on normal tissues, and also has the function of enhanced imaging contrast. The integrated diagnosis and treatment platform has good clinical transformation prospects, and is expected to promote the extensive exploration and application of new two-dimensional nanomaterials in tumor diagnosis and treatment and major diseases.

On this basis, the research team further developed the Nb2C MXene high-efficiency photothermal diagnostic agent for near-infrared NIR-I and NIR-II dual-zone response (J. Am. Chem. Soc., 2017, 139, 16235. DOI: 10.1021 / jacs.7b07818), the work for the first time involves the catalytic degradation of MXene enzyme, phagocytosis of MXene in vivo and in vitro, response to multi-region near-infrared light, efficient photothermal tumor therapy, diagnostic imaging, and the biological nature of the system Evaluation. The results of in vivo animal experiments show that Nb2C MXene nanophotothermal agent has no adverse effects on healthy mice within the evaluation period of 1 month, indicating that it has good in vivo biological safety. In the in vivo treatment study of tumor-bearing mice, it was found that both the tail vein injection and the intratumoral injection achieved the elimination of the xenograft tumor within a 15-day treatment cycle, and found that there was no recurrence within 1 month, indicating that the Nano-photothermal diagnostic agent has good biological safety and high-efficiency photothermal tumor ablation ability.

In addition, the research team has carried out a series of innovative research work in the use of two-dimensional biomedical materials, including the development of two-dimensional MnO2-based nanodiagnostic and therapeutic agents (Adv. Mater., 2014, 26, 7019-7026), and will soon The combination of two-dimensional black phosphorus nanosheets and 3D printed scaffolds not only utilizes the photothermal conversion ability of black phosphorus to kill tumor cells, but also promotes the repair of bone tissue with the effective chemical composition of black phosphorus (Adv. Mater., 2018, DOI: DOI: 10.1002 / adma.201705611). Based on the above research foundation, the research team was invited to publish three review papers in Chem. Soc. Rev. (2015), Nano Today (2016), Chem (2018), respectively elaborating two-dimensional graphene-based nano-biomaterials The research status and future development prospects of material chemistry in two-dimensional photothermal conversion biomaterials and two-dimensional nanobiomaterials have promoted the further clinical application of two-dimensional nanobiomaterials.

The above research work has received funding and support from the National Natural Science Foundation of China Key Projects, General Projects, Outstanding Youth Science Foundation Projects, and National Key R & D Program Young Subject Specialist Projects.

Two-dimensional Ta4C3 MXene nanosheet in vivo dual-mode PA / CT imaging and in vivo photothermal therapy integrated diagnosis and treatment integrated nano platform

Two-dimensional Nb2C MXene nanosheets‘ blood circulation half-life, body distribution, photothermal treatment effect evaluation and animal experimental treatment effect evaluation