In our previous work, we constructed a multifunction nano system SWNT-GC, which can synergize photothermal and immunological effects. To further improve the application of this system, we study the cytotoxicity of SWNT-GC and investigate the effects on malignant tumor therapy. Here, we selected the optimal concentration of GC and SWNTs for the stable SWNT-GC construction. No cytotoxicity was observed under the dose used in the experiments. Using mouse melanoma tumor model, Laser+SWNT-GC treatment resulted in a significant mice survival rate, there were no long-term survivors under other treatment. It is providing a promising treatment modality for the malignancy.
It has been known for a long time that microglial activation plays an important role in the pathology of neurodegenerative diseases. Once activated, they have macrophage-like capabilities, which can be detrimental by producing proinflammatory and neurotoxic factors including cytokines, reactive oxygen species (ROS) and nitric oxide that directly or indirectly cause neurodegeneration. Therefore, the regulation of microglial-induced neuroinflammation is considered a useful strategy in searching for neuroprotective treatments. In this study, our results showed that low power laser irradiation (LPLI) (20 J/cm<sup>2</sup>) could suppress microglial-induced neuroinflammation in LPS-activated microglia. We found that LPLI-mediated neuroprotection was achieved by activating tyrosine kinases Src, which led to MyD88 tyrosine phosphorylation, thus impairing MyD88-dependent proinflammatory signaling cascade. Our research may provide a feasible therapeutic approach to control the progression of neurodegenerative diseases.
Mounting evidence describes a more complex progress of macrophage activation during
photodynamic therapy (PDT), which performing distinct immunological functions and
different physiologies on surrounding cells and tissues. Macrophage-targeted PDT has been
applied in the selective killing of cells involved in inflammation and tumor. We have
previously shown that PDT-mediated tumor cells apoptosis can induce a higher level immune
response than necrosis, and enhance the macrophage activation. However, the molecular
mechanism of macrophage activation during PDT-induced apoptotic cells (AC) still unclear.
Here, we use confocal microscopy to image the phagocytosis of tumor cells by macrophages.
We also observed that PDT-treated AC can activate Toll-like receptors (TLRs) which are
present on macrophages surface. Besides, the increase in nitric oxide (NO) formation in
macrophages was detected in real time by a laser scanning microscopy. This study provided
more details for understanding the molecular mechanism of the immune response induced by
Phagocytosis and subsequent degradation of pathogens by macrophages play a pivotal role in host innate immunity
in mammals. Laser irradiation has been found to produce photobiological effects with evidence of interference with
immunological functions. However, the effects of laser on the immune response have not been extensively characterized.
In this study, we focused our attention on the effects of He-Ne laser on the phagocytic activity of macrophages by using
flow cytometry (FCM). After irradiating at fluence of 0, 1, 2 J/cm<sup>2</sup> with He-Ne laser (632.8 nm, 3mw), the cells were
incubated with microsphere and then subjected to FACS analysis. The results showed that Low-power laser irradiation
(LPLI) leads to an increase in phagocytosis on both mouse peritoneal macrophages and the murine macrophage-like cell
line RAW264.7. In addition, we demonstrated that LPLI increased phagocytosis of microsphere in a dose-dependent
manner, reaching a maximum at fluence of 2 J/cm<sup>2</sup>. Taken together, our results indicated that Low-power laser
irradiation with appropriate dosage can enhance the phagocytosis of macrophage, and provided a theoretical base for the
clinical use of the He-Ne laser.
It is well known that apoptotic cells (AC) participate in immune response. The immune response
induced by AC, either immunostimulatory or immunosuppressive, have been extensively studied.
However, the molecular mechanisms of the immunostimulatory effects induced by PDT-treated AC
remain unclear. Nitric oxide (NO) is an important signal transduction molecule and has been implicated
in a variety of functions. It has also been found to play an important role not only as a cytotoxic
effector but an immune regulatory mediator. In this study, we demonstrate that the PDT-induced
apoptotic tumor cells stimulate the production of NO in macrophages by up-regulating expression of
inducible nitric oxide synthase (iNOS). In addition, we show that AC, through toll-like receptors
(TLRs), can activate myeloid differentiation factor-88 (MyD88), indicating that AC serves as an
intercellular signal to induce iNOS expression in immune cells after PDT treatment. This study
provided more details for understanding the molecular mechanism of the immune response induced by
Nitric oxide (NO) is a biologically active molecule which has
multi-functional in different species. As a second
messenger and neurotransmitter, NO is not only an important regulatory factor between cells' information transmission,
but also an important messenger in cell-mediated immunity and cytotoxicity. On the other side, NO is involving in some
diseases' pathological process. In pathological conditions, the macrophages are activated to produce a large quantity of
nitric oxide synthase (iNOS), which can use L-arginine to produce an excessive amount of NO, thereby killing bacteria,
viruses, parasites, fungi, tumor cells, as well as in other series of the immune process. In this paper, photofrin-based
photodynamic therapy (PDT) was used to treat EMT6 mammary tumors <i>in vitro</i> to induce apoptotic cells, and then
co-incubation both apoptotic cells and macrophages, which could activate macrophage to induce a series of cytotoxic
factors, especially NO. This, in turn, utilizes macrophages to activate a cytotoxic response towards neighboring tumor
cells. These results provided a new idea for us to further study the immunological mechanism involved in damaging
effects of PDT, also revealed the important function of the immune effect of apoptotic cells in PDT.
Single-walled carbon nanotubes (SWNTs) have a high optical absorbance in the near-infrared (NIR) region. In this
special optical window, biological systems are known to be highly transparent. The optical properties of SWNTs provide
an opportunity for selective photothermal therapy for cancer treatment. The application of single-walled carbon
nanotubes (SWNTs) in the field of biomedicine is becoming an entirely new and exciting topic. Here, SWNTs are
conjugated to integrin αvβ3 monoclonal antibody, which can bind specifically to the surface of the tumor markers. In
vitro study revealed that SWNT-PEG-mAb presented a high targeting efficiency on integrin αvβ3-positive cells. Thus,
SWNTs, combined with suitable tumor markers, can be used as novel nanomaterials for selective photothermal therapy
for cancer treatment.
Recently, the long-term immunological effects of photodynamic therapy have attracted much attention. PDT induced
immune response was mainly initiated through necrotic cells and apoptotic cells, as well as immune cells such as
macrophages. Nitric oxide (NO) as an important regulatory factor in signal transfer between cells has been wildly
studied for generation, development, and metastasis of tumors. NO synthase is a key enzyme in nitric oxide synthesis.
However, inducible nitric oxide synthase (iNOS) is usually activated under pathological conditions, such as stress and
cancer, which can produce high levels of nitric oxide and contribute to tumor cytotoxicity. In addition, increased NO
production by iNOS has been associated with the host immune response and cell apoptosis, which play an important role
in many carcinogenesis and anti-carcinoma mechanisms. This study focuses on the NO production in macrophages,
induced by mouse breast carcinoma apoptotic cells treated by PDT in vitro, and on the effects of immune response
induced by apoptotic cells in tumor cells growth.
Apoptosis is an important cellular event that plays a key role in therapy of many diseases. The mechanisms of the
initiation and regulation of photodynamic therapy (PDT) -induced apoptosis is complex. Some PDT-associated
apoptosis pathways involved plasma membrane death receptors, mitochondria, lysosomes and endoplasmic reticulum
(ER). Our previous study found that Photofrin were localized primarily in mitochondria, the primary targets of
Photofrin-PDT. The key role of Bax in the mitochondrion-mediated apoptosis has been demonstrated in many systems.
In order to determine the role of Bax in the mitochondrion-mediated apoptosis induced by Photofrin-PDT, we used the
CFP/GFP-Bax plasmid to monitor the dynamics of Bax activation and translocation after PDT treatment. With laser
scanning confocal microscopy, we found that PDT induced Bax translocation from the cytosol to mitochondria; however,
with cells over-expressing YFP-HSP70 plasmids, Bax translocation was not detected. Thus, for Photofrin-PDT, Bax
activation and translocation were inhibited by HSP70, not influence the cell death.