German Applied Chemistry by Li Kai team of South University of science and technology：a small molecule photothermal agent with ultra-high photothermal conversion efficiency
At present, photothermal therapy (PTT) has become a hot spot in the research of new cancer treatment methods, and the development of photothermal agents with near-infrared absorption and high photothermal conversion efficiency (PTCE) is an important factor to achieve the ideal effect of PTT, which is of great significance to reduce the laser power density and study the photothermal treatment strategy at relatively low temperature. Based on this, Li Kai Group, Department of Biomedical Engineering, South University of science and technology, reported the design of a small molecular photothermal agent with high photothermal conversion efficiency and its application progress in low-temperature photothermal therapy with Hsp70 inhibition strategy.
In this work, the research group designed a new type of organic small molecule based on the photodynamic non adiabatic decline (PIND) effect, and realized the high-efficiency PTT tumor treatment at 43 ℃ stimulated by 808nm by using the inhibition of apoptozole (apo) on the expression of HSP70. When this kind of imine based molecular motor transits to the excited state under the irradiation of laser, it will be affected by the strong intramolecular twisted charge transfer (TICT) effect, which is beneficial to release energy back to the ground state in the non radiative decay way through the cone crossing (CI) process. This process can be regarded as a kind of light induced non adiabatic decay (PIND) phenomenon. Compared with the commercial probe ICG, this excited state molecule has almost no fluorescence release, so it can convert the light energy into heat energy more efficiently, showing up to 90% of the conversion efficiency.
In animal experiments, the authors 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 Figure 2a, after 8 hours of tail vein injection of c6ti / apo tat, mice were irradiated with 808nm laser, and the tumor site could be rapidly heated to 43 ° C, and stable in platform period. In c6ti / apo Tat and c6ti Tat mediated PTT tumor treatment experiments, the results showed that c6ti / apo Tat was significantly better than c6ti tat, and the tumor recurrence in c6ti / apo Tat treatment group was significantly lower than that in c6ti Tat treatment 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), it is 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, which proves the effectiveness of the combined treatment strategy. Therefore, the high-efficiency photothermal conversion molecular motor type photothermal agent reported in this study avoids the need of long alkyl chain or complex substituents in the traditional organic photothermal agent design. Combined with the inhibition mechanism of HSP70 expression, it effectively breaks through the limitations of traditional high-temperature PTT treatment and greatly reduces the effect of high-temperature ablation on normal tissues near the tumor The risk of thermal damage and so on provides a new idea for the development of small molecule high-efficiency photothermal agents.
Relevant work was published in angelw. Chem. Int. ed. Li Kai, associate professor of Biomedical Engineering Department of South University of science and technology, is the corresponding author, Ni Jianxiang, associate professor of research, is the first author of the paper, Zhang Xun is the co first author, and Yang Guang, Kang Tianyi, members of the research group, have made important contributions. The research team also paid special thanks to NSFC and Shenzhen Science and technology innovation Commission for their support.
Website of the research group:
Li Kai, Associate Professor
Ni Jianxiang, Associate professor of research