Graphene with unique physical and chemical properties has shown various potential applications in biomedicine. In this work, a photosensitizer molecule, Chlorin e6 (Ce6), is loaded on polyethylene glycol (PEG)-functionalized graphene oxide (GO) via supramolecular π-π stacking. The obtained GO-PEG-Ce6 complex shows excellent water solubility and is able to generate cytotoxic singlet oxygen under light excitation for photodynamic therapy (PDT). Owing to the significantly enhanced intracellular trafficking of photosensitizers, our GO-PEG-Ce6 complex offers a remarkably improved cancer cell photodynamic destruction effect compared to free Ce6. More importantly, we show that the photothermal effect of graphene can be utilized to promote the delivery of Ce6 molecules by mild local heating when exposed to a near-infrared laser at a low power density, further enhancing the PDT efficacy against cancer cells. Our work highlights the promise of using graphene for potential multifunctional cancer therapies.

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The study supports the theory that cancer metastasis is a highly selective dynamic process and the cell model system could be a useful platform for the study of HCC metastasis.

IL-33 may play a role in the vascular remodelling of hypoxic pulmonary hypertension (PH) but the precise mechanisms are still unclear. We hypothesized that hypoxia promotes expression of IL-33 and its receptor ST2 on vascular endothelial cells, which in turn leads to dysfunction of vascular endothelial cells and smooth muscle cells contributing to PH. Immunohistochemistry showed that immunoreactivity for IL-33 and ST2 was significantly increased in lung tissue of murine model of hypoxia-induced PH (HPH) and of subjects with bronchiectasis-PH. trans-Thoracic echocardiography showed that haemodynamic changes and right ventricular hypertrophy associated with HPH were significantly abrogated in St2−/− compared with WT mice. Administration of IL-33 further exacerbated these changes in the hypoxia-exposed WT mice. In vitro, hypoxia significantly increased IL-33/ST2 expression by human pulmonary arterial endothelial cells (HPAECs), while exogenous IL-33 enhanced proliferation, adhesiveness and spontaneous angiogenesis of HPAECs. Knockdown of endogenous Il33 or St2 using siRNA transfection significantly suppressed these effects in both normoxic and hypoxic culture-conditions. Deletion of the St2 gene attenuated hypoxia-induced, elevated lung expression of HIF-1α/VEGFA/VEGFR-2/ICAM-1, while administration of exogenous VEGFA partially reversed the attenuation of the haemodynamic indices of PH. Correspondingly, knockdown of the St2 or Hif1α genes almost completely abrogated IL-33-induced expression of HIF-1α/VEGFA/VEGFR-2 by HPAECs in vitro. Further, IL-33-induced angiogenesis by HPAECs was extensively abrogated by knockdown of the Hif1α/Vegfa or Vegfr2 genes. These data suggest that hypoxia induces elevated expression of IL-33/ST2 by HPAECs which, at least partly by increasing downstream expression of HIF-1α and VEGF initiates vascular remodelling resulting in HPH.

Triplet-triplet-annihilation-based upconversion (TTA-UC) imaging boasts a low-excitation irradiance and an uncanny lack of autofluorescence interference. Because of these promising features, this approach has been the subject of intensifying investigation. Despite the ideal features, the classical approach of TTA-UC imaging suffers from some crucial drawbacks. A major deficiency of the system lies within its poor photostability, especially for a near-IR-excitation system. Here we report a reduction strategy to improve the TTA-UC photostability. The poor photostability of TTA-UC can be attributed to singlet oxygen generation by the sensitizer under irradiation. We control the singlet oxygen by including a reductive solvent, which consumes the singlet oxygen, thereby improving the TTA-UC photostability. We also prepared TTA-UC nanocapsules with reductive solvent soybean oil inside. In comparison to nonreductive solvents such as toluene, our system shows a significant enhancement to the TTA-UC photostability. The prepared TTA-UC nanocapsules were then used for whole-animal deep imaging with a high signal-to-noise ratio.