Gold-nanorods-siRNA nanoplex for improved photothermal therapy by gene silencing.

Nanomaterials-mediated photothermal therapy (PTT) often suffers from the fundamental cellular defense mechanism of heat shock response which leads to therapeutic resistance of cancer cells and reduces the therapeutic efficacy. Herein, a gold nanorods (GNRs)-siRNA platform with gene silencing capability is produced to improve the PTT efficiency. After surface modification, the GNRs show the ability to deliver siRNA oligos targeting BAG3 which is an efficient gene to block the heat-shock response. The synthesized GNRs-siRNA nanoplex exhibits excellent ability in the delivery of siRNA into cancer cells with high silencing efficiency which is even better than that of commercial Lipofectamine 2000. The in vitro and in vivo studies demonstrate the ability of the GNRs-siRNA nanoplex to sensitize the cancer cells to PTT under moderate laser irradiation by down-regulating the increased BAG3 expression and enhancing apoptosis. The GNRs-siRNA mediated PTT has large potential in clinical cancer therapy due to the elimination of therapeutic resistance and enhanced photothermal therapeutic efficacy by means of gene silencing. It also suggests an efficient platform for gene delivery and controllable gene therapy.

O2 and Ca(2+) fluxes as indicators of apoptosis induced by rose bengal-mediated photodynamic therapy in human oral squamous carcinoma cells.

OBJECTIVE: Photodynamic therapy (PDT) triggers various cellular responses and induces cell death via necrosis and/or apoptosis. This study evaluated the feasibility of using O2 and Ca(2+) fluxes as indicators of apoptosis induced by rose bengal (RB)-mediated PDT in human oral squamous carcinoma cells (Cal27 cells). METHODS: Intracellular reactive oxygen species (ROS) generation was assessed by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) method. Real-time O2 and Ca(2+) flux measurements were performed using the noninvasive micro-test technique (NMT). Apoptosis of the PDT-treated cells was confirmed by 4'6-diamidino-2-phenylindole-dilactate staining. The activation of apoptosis-related molecules was examined using Western blot. We assayed the effects of the fluctuation of O2 and Ca(2+) flux in response to PDT and the apoptotic mechanism, by which ROS, O2, and Ca(2+) synergistically may trigger apoptosis in PDT-treated cells. RESULTS: Real-time O2 and Ca(2+) flux measurements revealed that these indicators were involved in the timely regulation of apoptosis in the PDT-treated cells and were activated 2 h after PDT treatment. RB-mediated PDT significantly elicited the generation of ROS by approximately threefold, which was critical for PDT-induced apoptosis. Cytochrome c and cleaved caspase-3, caspase-9 and poly ADP ribose polymerase (PARP) were overexpressed, and the data provided evidence that 2 h was considered to be the key observation time in RB-mediated PDT-induced apoptosis in Cal27 cells. CONCLUSIONS: Our collective results indicated that the effects of O2 and Ca(2+) fluxes may act as a real-time biomonitoring system of apoptosis in the RB-PDT-treated cells. Also, RB-mediated PDT can be a potential and effective therapeutic modality in oral squamous cell carcinoma.

Rose-bengal-conjugated gold nanorods for in vivo photodynamic and photothermal oral cancer therapies.

Gold nanorods (GNRs) conjugated with rose bengal (RB) molecules exhibit efficient singlet oxygen generation when illuminated by 532 nm green light and high photothermal efficiency under 810 nm near-infrared (NIR) irradiation. In vitro experiments show that reactive oxygen species generated by green light and hyperthermia produced by NIR light constitute two different mechanisms for cancer cell death. The RB-GNRs also exhibit improved photodynamic efficacy by enhancing the uptake of RB by cancer cells. In vivo experiments are conducted on hamster cheek pouches to resemble the human oral cancer conditions more accurately to assess the therapeutic effectiveness. Compared to the single photodynamic therapy (PDT) or photothermal therapy (PTT), the RB-GNRs with combined PDT-PTT capabilities provide better therapeutic effects against oral cancer and have large potential in cancer treatment.

Inhibitory effect of flavonoid baicalin on degranulation of human polymorphonuclear leukocytes induced by interleukin-8: potential role in periodontal diseases.

Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to possess anti-inflammatory activity through its ability to complex with chemokines and thus reduces the capacity of chemokines to bind and activate their receptors. In the present study, we investigated whether baicalin could block polymorphonuclear leukocytes (PMNs) degranulation induced by interleukin (IL)-8, a CXC chemokine. Human PMNs were isolated from the peripheral blood of periodontal healthy donors and incubated with various concentrations of IL-8 (preincubated with or without baicalin). The morphology of PMNs was examined by transmission electron microscopy and extracellular concentration of granule component matrix metalloproteinase-8 (MMP-8) was detected by enzyme-linked immunosorbent assay (ELISA). Results showed that IL-8 could significantly induce MMP-8 release from PMNs when compared to control, and its inductive activity was concentration-dependent. But when preincubated with various concentrations of baicalin, the amount of MMP-8 release from PMNs decreased significantly. The present study concludes that baicalin could block MMP-8 release from PMNs induced by IL-8, which suggests that it may play an important role in the prevention and treatment of periodontal disease.