Carbon Dots with Absorption Red-Shifting for Two-Photon Fluorescence Imaging of Tumor Tissue pH and Synergistic Phototherapy.

Phototherapy exhibits significant potential as a novel tumor treatment method, and the development of highly active photosensitizers and photothermal agents has drawn considerable attention. In this work, S and N atom co-doped carbon dots (S,N-CDs) with an absorption redshift effect were prepared by hydrothermal synthesis with lysine, o-phenylenediamine, and sulfuric acid as raw materials. The near-infrared (NIR) absorption features of the S,N-CDs resulted in two-photon (TP) emission, which has been used in TP fluorescence imaging of lysosomes and tumor tissue pH and real-time monitoring of apoptosis during tumor phototherapy, respectively. The obtained heteroatom co-doped CDs can be used not only as an NIR imaging probe but also as an effective photodynamic therapy/photothermal therapy (PDT/PTT) therapeutic agent. The efficiencies of different heteroatom-doped CDs in tumor treatment were compared. It was found that the S,N-CDs showed higher therapeutic efficiency than N-doped CDs, the efficiency of producing 1O2 was 27%, and the photothermal conversion efficiency reached 34.4%. The study provides new insight into the synthesis of carbon-based nanodrugs for synergistic phototherapy and accurate diagnosis of tumors.

A tumor microenvironment-induced absorption red-shifted polymer nanoparticle for simultaneously activated photoacoustic imaging and photothermal therapy.

Tumor microenvironment-responsive therapy has enormous application potential in the diagnosis and treatment of cancer. The glutathione (GSH) level has been shown to be significantly increased in tumor tissues. Thus, GSH can be used as an effective endogenous molecule for diagnosis and tumor microenvironment-activated therapy. In this study, we prepared a tumor microenvironment-induced, absorption spectrum red-shifted, iron-copper co-doped polyaniline nanoparticle (Fe-Cu@PANI). The Cu(II) in this nanoparticle can undergo a redox reaction with GSH in tumors. The redox reaction induces a red shift in the absorption spectrum of the Fe-Cu@PANI nanoparticles from the visible to the near-infrared region accompanying with the etching of this nanoparticle, which simultaneously activates tumor photoacoustic imaging and photothermal therapy, thereby improving the accuracy of in vivo tumor imaging and the efficiency of photothermal therapy. The nanoparticle prepared in this study has broad application prospects in the diagnosis and treatment of cancer.

Dual functionalized natural biomass carbon dots from lychee exocarp for cancer cell targetable near-infrared fluorescence imaging and photodynamic therapy.

Photodynamic therapy (PDT) is a non-invasive phototherapy that has gained significant attention for cancer therapy. However, image-guided PDT still remains a considerable challenge. Herein, we developed a targeted, near-infrared (NIR) fluorescence imaging nanoprobe for cancer cells by preparing natural biomass carbon dots (NBCDs) from lychee exocarp, and loading transferrin and a photosensitizer on the NBCD surfaces for image-guided PDT of cancer cells and mouse tumors. Because the surfaces of cancer cells exhibit more transferrin receptors, the proposed NIR fluorescent nanoprobe can better penetrate cancer cells for cancer cell targetable fluorescence imaging. Thus, the dual-function nanoprobe made from natural biomass can be used as a specific agent for NIR fluorescence imaging and PDT. More importantly, the functional nanoprobe prepared from natural biomass emits NIR fluorescence, shows very low biological toxicity, and can minimize side effects on normal cells. After directly injecting the nanoprobes into tumor tissues, the photosensitizers on the surface of the NBCDs can produce singlet oxygen (1O2) through photodynamic reactions when irradiated with 650 nm light to kill cancer cells, thus inhibiting tumor growth in PDT-treated mice. Therefore, the functional fluorescent nanoprobe made from natural biomass has been employed as a PDT agent, and holds great promise in image-guided tumor PDT.

High-sensitive electrochemical detection of point mutation based on polymerization-induced enzymatic amplification.

Here a highly sensitive electrochemical method is described for the detection of point mutation in DNA. Polymerization extension reaction is applied to specifically initiate enzymatic electrochemical amplification to improve the sensitivity and enhance the performance of point mutation detection. In this work, 5'-thiolated DNA probe sequences complementary to the wild target DNA are assembled on the gold electrode. In the presence of wild target DNA, the probe is extended by DNA polymerase over the free segment of target as the template. After washing with NaOH solution, the target DNA is removed while the elongated probe sequence remains on the sensing surface. Via hybridizing to the designed biotin-labeled detection probe, the extended sequence is capable of capturing detection probe. After introducing streptavidin-conjugated alkaline phosphatase (SA-ALP), the specific binding between streptavidin and biotin mediates a catalytic reaction of ascorbic acid 2-phosphate (AA-P) substrate to produce a reducing agent ascorbic acid (AA). Then the silver ions in solution are reduced by AA, leading to the deposition of silver metal onto the electrode surface. The amount of deposited silver which is determined by the amount of wild target can be quantified by the linear sweep voltammetry (LSV). The present approach proved to be capable of detecting the wild target DNA down to a detection limit of 1.0×10(-14) M in a wide target concentration range and identifying -28 site (A to G) of the ß-thalassemia gene, demonstrating that this scheme offers a highly sensitive and specific approach for point mutation detection.

[Effect of tongxinluo ultramicro-pulverization on myocardial post-reperfusion no-reflow in mini-swine model of acute myocardial infarction].

OBJECTIVE: To assess the effect of Tongxinluo (TXL) ultramicro-pulverization in preventing and treating post-reperfusion no-reflow in mini-swine model of acute myocardial infarction. METHODS: Forty mini-swines were randomly divided into 5 groups, the control group, the three (low-, middle- and high-dose) TXL groups and the sham-operation group, with 8 in each group. After pigs in the three TXL groups were administered with TXL in a dose of 0.05g/kg, 0.2g/kg and 0.5g/kg once a day for 3 days respectively, they were made into acute myocardial ischemia/reperfusion model by ligating left anterior descending coronary artery for 3h followed with 1h of untying. Hemodynamic examination and myocardial contrast echocardiography (MCE) were conducted before and after ligation, and after reperfusion, finally, pathological analysis was done. RESULTS: Post-reperfusion ventricular function injury was significantly improved in the three TXL groups, as compared with the control group, the no-reflow area determined by hemodynamic and MCE decreased from 78.5 +/- 4.4% and 82.3 +/- 1.9% in control to 43.4 +/- 3.2% and 44.6 +/- 3.3% (low-dose), 25.2 +/- 2.4% and 25.7 +/- 4.0% (middle-dose), 24.0 +/- 1.9% and 24.9 +/- 4.2% (high-dose), respectively (P < 0.05 or P < 0.01), and the myocardial infracted area was reduced from 98.5 +/- 1.4% to 89.8 +/- 4.6%, 80.2 +/- 3.1% and 79.9 +/- 3.1%, respectively (P < 0.05, P < 0.01). CONCLUSION: TXL ultramicro-pulverization can effectively prevent and treat no-reflow after myocardial acute infarction following reperfusion, and reduce the infracted area.