Bupivacaine inhibits the malignant biological behavior of oral squamous cell carcinoma cells by inhibiting the activation of ERK1/2 and STAT3.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an aggressive malignant tumor. Bupivacaine (Bupi), a local anesthetic drug, has been shown to display anti-tumor activity against a variety of tumors. METHODS: We selected OSCC CAL-27 cells as the in vitro model. Cell toxicity, proliferation, apoptosis, and stemness were conducted, respectively. The protein levels of Ki67, PCNA, caspase-3, caspase-9, survivin, SOX2, NANOG, OCT4, STAT3, p-STAT3, ERK1/2, and p-ERK1/2 were evaluated by western blotting. Male BALB/c nude mice xenograft model was used to evaluate the effect of Bupi on tumor growth in vivo. RESULTS: Compared with the control group, Bupi (0.2, 0.5, or 1 µm) significantly decreased the cell viability and the proliferation of CAL-27 cells. Meanwhile, Bupi significantly promoted apoptosis of CAL-27 cells compared with the control group. Additionally, Bupi inhibited the stemness of CAL-27 cells which was evidenced by a sphere formation assay. Bupi decreased the phosphorylation level of STAT3 and ERK1/2 in a dose-dependent manner. The addition of interferon-γ (IFN-γ, 20 ng/mL) in the experiment verified the role of Bupi on STAT3 and ERK1/2 signaling. In vivo, Bupi (40 µmol/kg) obviously suppressed the weight and size of the xenograft tumor, the number of apoptotic cells and Ki67+ decreased. Also, Bupi treatment inhibited the expression of stem-like marker proteins. CONCLUSIONS: Bupi could be used as an anticancer drug against the growth and stemness ability of OSCC. The underlying mechanism may be due to down-regulation of STAT3 and ERK1/2 signaling. This study provides a new insight for the application of Bupi.

Pheophytin Derived Near-Infrared-Light Responsive Carbon Dot Assembly as a New Phototheranotic Agent for Bioimaging and Photodynamic Therapy.

Carbon dots (CDs), a kind of phototheranostic agent with the capability of simultaneous bioimaging and phototherapy [i.e., photodynamic therapy (PDT) or photothermal therapy (PTT)], have received considerable attention because of their remarkable properties, including flexibility for surface modification, high biocompatibility, low toxicity and photo-induced activity for malignant tumor cells. Among numerous carbon sources, it has been found that natural biomass are good candidates for the preparation of CD phototheranostic agents. In this study, pheophytin, a type of Mg-free chlorophyll derivative and also a natural product with low toxicity, was used as a raw carbon source for the synthesis of CDs by using a microwave method. The obtained hydrophobic CDs exhibited a maximum near-infrared (NIR) emission peak at approximately 680 nm, and high singlet oxygen (1 O2 ) generation with a quantum yield of 0.62. The self-assembled CDs from the as-prepared CDs with DSPE-mPEG2000 retained efficient 1 O2 generation. The obtained carbon dot assembly was not only an efficient fluorescence (FL) imaging agent but also a smart PDT agent. Our studies indicated that the obtained hydrophilic CD assembly holds great potential as a new phototheranostic agent for cancer therapy. This work provides a new route for synthesis of CDs and proposes a readily available candidate for tumor treatment.

New detection method for nucleoside triphosphates based on carbon dots: The distance-dependent singlet oxygen trapping.

The distance-dependent based sensing mechanism, such as fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) absorption of gold nanoparticles, has been used widely in visual detection. In this work, we report another distance-dependent detection method for nucleoside triphosphates (NTPs) based on carbon dots (CDs) (1O2 donor) and 9, 10-diphenylanthracene-2-boronic acid (DABA, 1O2 acceptor). The CDs can generate singlet oxygen (1O2) which allows diffusion within 200 nm. Thus, the distance between CDs and DABA decreased through binding of NTPs (<200 nm), leading to absorption changes of DABA under light irradiation due to 1O2 trapping. This sensing system (CDs@DABA) has high selectivity for the detection of NTPs due to the double molecular recognition and a linear response in the 0-80 µM concentration range was accomplished with the detection limit as low as 4.35 µM.

Synthesis of carbon dots from Hypocrella bambusae for bimodel fluorescence/photoacoustic imaging-guided synergistic photodynamic/photothermal therapy of cancer.

As phototheranostic agents, carbon dots (CDs), have recently drawn considerable attention due to their excellent physicochemical properties. However, the complex synthetic route and high-cost of CDs greatly limit their practical application. To address this issue, given their nearly infinite supply from nature, Hypocrella bambusae is used as the precursor for the preparation of CDs in this study. The obtained Hypocrella bambusae CDs (HBCDs) possess good water solubility, broad absorption (350-800 nm), red-light emission (maximum peak at 610 nm), and low biotoxicity. Moreover, HBCDs can highly generate 1O2 (0.38) and heat (27.6%) under 635 nm laser irradiation. These excellent properties of HBCDs capacitate them to be utilized for bimodal fluorescence/photoacoustic imaging-guided synergistic photodynamic therapy (PDT)/photothermal therapy (PTT). This work provides a new candidate for tumor treatment with the combination of PDT and PTT, and explores a novel approach for the preparation of CD-based phototheranostic agents with natural biomass as raw carbon sources.

A Magnetofluorescent Carbon Dot Assembly as an Acidic H2 O2 -Driven Oxygenerator to Regulate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy.

Recent studies indicate that carbon dots (CDs) can efficiently generate singlet oxygen (1 O2 ) for photodynamic therapy (PDT) of cancer. However, the hypoxic tumor microenvironment and rapid consumption of oxygen in the PDT process will severely limit therapeutic effects of CDs due to the oxygen-dependent PDT. Thus, it is becoming particularly important to develop a novel CD as an in situ tumor oxygenerator for overcoming hypoxia and substantially enhancing the PDT efficacy. Herein, for the first time, magnetofluorescent Mn-CDs are successfully prepared using manganese(II) phthalocyanine as a precursor. After cooperative self-assembly with DSPE-PEG, the obtained Mn-CD assembly can be applied as a smart contrast agent for both near-infrared fluorescence (FL) (maximum peak at 745 nm) and T1 -weighted magnetic resonance (MR) (relaxivity value of 6.97 mM-1 s-1 ) imaging. More interestingly, the Mn-CD assembly can not only effectively produce 1 O2 (quantum yield of 0.40) but also highly catalyze H2 O2 to generate oxygen. These collective properties of the Mn-CD assembly enable it to be utilized as an acidic H2 O2 -driven oxygenerator to increase the oxygen concentration in hypoxic solid tumors for simultaneous bimodal FL/MR imaging and enhanced PDT. This work explores a new biomedical use of CDs and provides a versatile carbon nanomaterial candidate for multifunctional nanotheranostic applications.