Angelw: two dimensional single element germanium quantum dots -- a new anticancer photothermal nanodrug

Photothermal therapy (PTT) is a non-invasive cancer treatment strategy, which uses near-infrared photothermal agents (PTAs) to generate local high heat by light energy, so as to eliminate tumor At present, the synthesis of PTAs with high photothermal conversion efficiency and good biocompatibility is still a challenge Because of its wide absorption band, ultra-high surface volume ratio, easy synthesis, convenient modification, simple metabolism and degradation mechanism, two-dimensional single material has become a potential PTA The two-dimensional single element germanium material has more advantages than the traditional graphene and black phosphorus, because its absorption band is wider (uv-nir), and its biological safety is better (it is the trace element that is vital to human health) However, the traditional synthesis methods of Ge based nanomaterials are either unable to obtain two-dimensional materials or inefficient Based on this, Professor Omid C farokhzad, Dr Tao Wei and Professor Sui xinbing of Hangzhou Normal University and their collaborators developed a new method of bottom-up synthesis of ultra-small two-dimensional germanium quantum dots (geqds) based on ultrasound (Figure 1a) The geqds modified by polyethylene glycol has high efficiency of photothermal conversion, good stability and excellent biocompatibility At the same time, it has the characteristics of multimodal imaging (near-infrared fluorescence imaging, photoacoustic imaging, photothermal imaging), which can be used for non-invasive guidance and real-time imaging of tumor treatment Relevant research results were recently published on angelw Chem Int ed (DOI: 10.1002 / anie 201908377) Geqds was synthesized by ultrasonic synthesis of germanium powder in isopropanol, and a series of modifications and characterization (Figure 1) were carried out The results of TEM and AFM showed that geqds were 4.5 nm in size and 2.2 nm in thickness Because this geqds is easy to precipitate in high salt solution, the peg @ geqds modified by PEG was obtained by DSPE-PEG Peg @ geqds did not precipitate after incubation in PBS and culture medium for 24 hours FTIR analysis showed that PEG modification was successful The crystal structures of geqds and PEG @ geqds were determined by Raman and XRD analysis Further absorption spectrum analysis shows that the absorption band of PEG @ geqds is similar to other two-dimensional materials, and its near-infrared spectral extinction coefficient at 808 nm is 5.333 LG-1 cm-1, which is significantly higher than other PTAs (photo source: angelw Chem Int ed.) the photothermal properties of PEG @ geqds with different concentrations were analyzed by using 808 nm laser (Figure 2) It was found that PEG @ geqds showed photothermal effect depending on concentration and laser intensity, and its photothermal conversion efficiency (45.9%) was much higher than other PTAs Compared with some materials with higher photothermal conversion efficiency, the synthesis method of PEG @ geqds is simpler and cheaper Next, the photothermal stability of PEG @ geqds was studied with ICG as a control The results showed that the photothermal stability of PEG @ geqds was significantly better than that of ICG The biocompatibility (Figure 3) of PEG @ geqds was studied by hemolysis and cytotoxicity experiments The results showed that PEG @ geqds did not cause significant hemolysis (less than 8%) within 8 hours, and there was no significant cytotoxicity within 48 hours, which initially proved that PEG @ geqds had good biocompatibility Peg @ geqds will be swallowed into the cells soon after incubation with cancer cells More than 85% of breast cancer cells will die in 5 minutes (808 nm, 1 W / cm2, 2200 μ g / ml) of light, which is mainly due to the photothermal effect that leads to mitochondrial dysfunction and changes in mitochondrial membrane potential (image source: angelw Chem Int ed.) (image source: angelw Chem Int ed.) the author then evaluated the in vivo distribution of PEG @ geqds (Figure 4) In vivo near-infrared fluorescence imaging and photoacoustic imaging experiments showed that PEG @ geqds was the most abundant tumor after 24 hours of intravenous injection into mice The authors then evaluated the efficacy of PEG @ geqds in the treatment of tumors After 24 hours of intravenous injection of PEG @ geqds into 4T1 tumor bearing mice, the tumor site was irradiated by 808 nm laser After 5 minutes, the temperature of the tumor increased by 20 ℃, while that of the control group only increased by 4 ℃ After PEG @ geqds and near-infrared light treatment, the tumor almost disappeared, but the growth rate of mice without peg @ geqds injection or near-infrared light treatment was the same as that of the control group This shows that PEG @ geqds and near-infrared light have no therapeutic effect, but under near-infrared light, the photothermal effect of PEG @ geqds can significantly inhibit the growth of tumor, or even completely eliminate the tumor In vivo biocompatibility analysis showed that PEG @ geqds had no acute or chronic toxicity to normal organs, which initially proved that the quantum dots had good biocompatibility (picture source: angelw Chem Int ed.) in general, this study is the first time to synthesize two-dimensional single element germanium quantum dots by a simple and convenient method for photothermal therapy of tumors After PEG modification, the quantum dots have excellent stability, biosafety and photothermal conversion efficiency The quantum dots are smaller in size, so they can penetrate deeper into tumor tissue In addition, under the guidance of near-infrared fluorescence imaging and photoacoustic imaging, it can achieve accurate photothermal treatment of tumor tissue and effectively remove tumor Therefore, this new quantum dot material with low price, convenient synthesis and excellent biocompatibility has great potential in the future clinical transformation.