Li Kai research group of South University of science and technology published research results of hypothermia photothermotherapy in German Applied Chemistry

2020-05-27

Recently, Li Kai, associate professor of Biomedical Engineering Department of South University of science and technology, has made the latest progress in the research on the mechanism of small molecule photothermal agents and its application in low temperature photothermal therapy with Hsp70 inhibition strategy. The research results were published on the title of "photoinduced nonadiabatic decision guided molecular motor triggers effective photothermal conversion for Hypertermia cancer therapy", the top international journal of chemistry, angelwandte Chemistry International Edition.

Photothermal therapy (PTT) has become an important research direction of cancer treatment. However, at present, the traditional PTT is facing many limitations, such as the complex synthesis of inorganic / organic photothermal agents (PTA), the high dependence of laser power density, the high temperature PTT is easy to cause normal tissue damage and other side effects. Therefore, it is of great significance to develop a new PTT strategy at low temperature (43 ℃). In this work, we designed a novel organic small molecule based on the photodynamic non adiabatic decay (PIND) effect, and realized the 43 ℃ high-efficiency PTT tumor treatment under the low power density of 808 nm laser by using the inhibition of apoptozole (apo) on the expression of HSP70.

Ni Jianxiang, associate professor of Biomedical Engineering Department and Research Institute of frontier and interdisciplinary sciences, introduced that the new organic small molecule developed this time is an imine based molecular motor. When the imine based molecular motor transits to the excited state due to laser irradiation, it will be affected by the strong intramolecular twisted charge transfer (TICT) effect, which helps it cross the cone( CI) process, in which energy is released back to the ground state in a non radiative manner, can be regarded as a light induced non adiabatic decay (PIND) phenomenon. Compared with the commercial probe ICG, this kind of excited state molecule has almost no fluorescence release, so it can convert the light energy into heat energy more perfectly, and achieve the conversion efficiency of up to 90%.

In the aspect of animal experiments, the research group constructed a heat responsive tumor cell delivery system by nanoprecipitation and surface modification of cell membrane penetrating peptide, and used 4T1 subcutaneous transplanted tumor of nude mice as tumor model to study the therapeutic effect of c6ti / apo Tat nanoparticle mediated low-temperature PTT tumor. As shown in Fig. 2a, after 8 hours of tail vein injection of c6ti / apo tat, mice were irradiated with 808 nm laser (0.5 w cm-2), and the tumor site was rapidly heated to 43 ℃, and stable in platform period. The results showed that the therapeutic effect of c6ti / apo Tat was significantly better than that of c6ti tat, and the tumor recurrence of c6ti / apo Tat group was significantly lower than that of c6ti Tat group (Fig. 2B, 2C). Through the analysis of HSP70 immunohistochemistry and TUNEL histochemical staining in situ tumor tissue sections of the two treatment groups (Fig. 2D), the research group found that apo released by heat trigger can effectively inhibit the expression of HSP70 in tumor cells, resulting in the apoptosis rate of c6ti / apo Tat mediated low-temperature PTT tumor cells significantly higher than that of c6ti Tat treatment group, proving the effectiveness of the combined treatment strategy. Therefore, this study developed a new high-efficiency photothermal conversion molecular motor, which avoids the traditional photothermal agents need to use long alkyl chain or complex substituent synthesis, combined with the inhibition mechanism of HSP70 expression, effectively breaking through the limitations of traditional high-temperature PTT treatment, and providing a new idea for the development of small molecular high-efficiency photothermal agents.

Southern University of science and technology is the first communication unit of the paper, Ni Jianxiang is the first author of the paper, Li Kai is the only communication author, and Yang Guang, Kang Tianyi, Cha Menglei and Li Jianxi, members of the research group, are co authors. The research was supported by NSFC and Shenzhen basic research plan.

paper link :

https://www.onlinelibrary.wiley.com/doi/10.1002/anie.202002516