Cancer Phototherapy via Type I PDT (photodynamic therapy) and PTT (photothermal therapy)

Cancer is one of the major diseases that seriously affect the safety of human life. Traditional cancer treatment methods have problems such as large trauma, high toxicity, side effects, and easy recurrence. In recent years, photodynamic therapy ( PDT ) and photothermal therapy ( PTT ) have shown great potential in tumor therapy due to their advantages of non-invasiveness, high selectivity, and few side effects. Although the current research on photo diagnostic reagents has made some progress, most of them are type II photosensitizers that are highly dependent on oxygen. Therefore, the problem of tumor hypoxia seriously affects the therapeutic effect of type II PDT.

Recently, the team of Academician Tang Benzhong of the Chinese University of Hong Kong (Shenzhen) and Professor Wang Jianguo of Inner Mongolia University published a paper entitled "Acceptor Planarization and Donor Rotation: A Facile Strategy for Realizing Synergistic Cancer Phototherapy via Type I PDT and PTT " in the journal " ACS Nano ". Article (DOI: /acsnano.1c10019 ). The research team proposed a molecular design strategy of " acceptor planarization and donor rotation " to construct near-infrared luminescent type I AIE phototherapeutic molecules with high photothermal conversion efficiency and reactive oxygen species generation ability. Among them, the planarization of the receptor at the molecular center can effectively increase the degree of molecular conjugation, promote the red-shift of the absorption and emission wavelengths of the photosensitizer, and also adjust the excited triplet energy level of the photosensitizer to match the energy level of the biological substrate, to realize the transformation of the photosensitizer type from type II to type I. Secondly, the introduction of twisted large sterically hindered donor groups at both ends of the molecular skeleton can effectively prevent the fluorescence quenching of the photosensitizer in the aggregated state without affecting the conjugation degree of the photosensitizer. It is also possible to increase the non-radiative transition pathways of aggregated photosensitizers, thereby increasing the photothermal conversion efficiency (Figure. 1).

Figure 1. Schematic illustration of the design strategy of vinyl-based DPP photosensitizers and their synergistic therapy for type I PDT/ PTT tumors guided by near-infrared fluorescence.

Studies have shown that when the thiophene group in the traditional type II photosensitizer 3,6 - dithiophene -substituted diketopyrrolopyrrole ( DPP ) derivative is repalced to a vinyl group, the acceptor unit of the photosensitizer molecule tends to be almost planar, Strong intramolecular charge transfer and DA interactions were formed within the molecule (Fig. 2 ). Therefore, compared with thiophene-based DPP photosensitizers, vinyl DPP photosensitizers all have longer near-infrared absorption and emission wavelengths and turn into type I photosensitizers Figure 3. Their photothermal conversion efficiencies gradually increased from 55% to 66% as the number of donor groups increased. In vivo experiments in mice confirmed that the vinyl DPP photosensitizer (2TPEVDPP ) with the highest number of rotors has specific targeting imaging ability for tumors and showed a good synergistic treatment effect of type I PDT/PTT Figure 4. This study provides a reference for overcoming the hypoxia problem in tumor treatment and for the development of near-infrared type I phototherapy molecules.

Figure 2. (A) The chemical structures of the four photosensitizers ; (B) the optimized molecular structures, HOMO and LUMO energy levels of the four photosensitizers ; (C) twist angles in the molecular structures of the four photosensitizers .

Figure 3. Characterization of photodynamic and photothermal properties of photosensitizers. (A) Particle size and SEM image of 2TPEVDPP nanoparticles; (B) UV absorption spectrum (C) fluorescence spectrum ( D) ROS generation ability test diagram ( E ) singlet oxygen generation ability test diagram of photosensitizer nanoparticles (F) ESR signal diagram ( G ) superoxide anion production test diagram (H) ROS generation capacity intensity comparison diagram (I)  2TPEVDPP nanoparticles at different powers (J) and concentration (K​​) photothermal performance test, infrared thermal imaging photos of 2TPEVDPP nanoparticles at different concentrations; (L) 2TPEVDPP nanoparticles photothermal conversion efficiency.

Figure 4. (A) Schematic diagram of in vivo tumor diagnosis and treatment timetable; (B) in vivo fluorescence imaging images of mice after intravenous injection of 2TPEVDPP nanoparticles; (C) in vivo tissue and tumor NIR-I imaging images of 2TPEVDPP NPs 72 h after intravenous injection ; (D) Thermal image of 4T1 tumor-bearing mice under 0.5 Wcm−2 (660 nm) laser irradiation after intravenous injection of 2TPEVDPP nanoparticles or saline for 3 to 6 h ; (E) intravenous injection of 2TPEVDPP nanoparticles after the change of fluorescence intensity in mouse tumor area with time; (F) relative fluorescence intensity of tumor and major organs after 72 h of injection ; (G) relative tumor temperature change from 0-15 min after laser irradiation ; (H) Tumor volume change during treatment; (I) Different treatment groups after treatment Tumor photos in vitro ; (J) change of mouse body weight ; (K) Ki-67 , HIF-α , H&E staining of mouse tumors after treatment in different treatment groups.

Original link

Acceptor Planarization and Donor Rotation: A Facile Strategy for Realizing Synergistic Cancer Phototherapy via Type I PDT and PTT. Lina Feng, Chunbin Li, Lingxiu Liu, Zhiyi Wang, Zihan Chen, Jia Yu, Weiwei Ji, Guoyu Jiang*, Pengfei Zhang, Jianguo Wang*, and Ben Zhong Tang*

ACS Nano, 2022, 16, 3, 4162–4174. https://pubs.acs.org/doi/10.1021/acsnano.1c10019.

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