Our previous studies have demonstrated that as a mitochondria-targeting cancer phototherapy, high fluence low-power laser irradiation (HF-LPLI) induces mitochondrial superoxide anion burst, resulting in oxidative damage to tumor cells. In this study, we further explored the immunological effects of HF-LPLI-induced apoptotic tumor cells. When macrophages were co-incubated with apoptotic cells induced by HF-LPLI, we observed the increased levels of TNF-α secretion and NO production in macrophages. Further experiments showed that NF-κB was activated in macrophages after co-incubation with HF-LPLI-induced apoptotic cells, and inhibition of NF-κB activity by pyrrolidinedithiocarbamic acid (PDTC) reduced the elevated levels of TNF-α secretion and NO production. These data indicate that HF-LPLI-induced apoptotic tumor cells induce the secretion of pro-inflammatory cytokines in macrophages, which may be helpful for better understanding the biological effects of cancer phototherapy.
The combination of diagnostics and therapeutics is growing rapidly in cancer treatment. Here, using upconversion
nanoparticles coated with chitosan conjugated with a targeting molecule and loaded with indocyanine green (ICG), an
excitation-selectable nanoprobe with highly integrated functionalities, including the emission of visible and near-infrared
(NIR) light, strong optical absorption in the NIR region and high photostability was developed. After injected in mice, the
nanoprobes targeted to the tumor vascular system. NIR lasers (980 and 808 nm) were then selectively applied to the mice.
The results show that, the emitted upconversion fluorescence and NIR fluorescence can be used in a complementary
manner for high signal/noise ratio and sensitive tumor imaging for more precise tumor localization; Highly effective
photothermal therapy can be realized using 808 nm laser irradiation. The upconversion fluorescence at 654 nm is useful for
monitoring treatment effect during thermal therapy. In summary, using the nanoprobes, outstanding therapeutic efficacy
could be realized and the nanofabrication strategy would highlight the promise of upconversion nanoparticles in cancer
theranostics.
Reactive oxygen species (ROS) produced by photodynamic therapy (PDT) is recorded in vivo using a chemiluminescence (CL)-based gated optical system. A novel approach is developed to utilize the fluorescence (FL) of the CL probe as an internal fluorescence to calibrate the observed CL on pharmacokinetics of the probe in situ. The results show that during an in vivo PDT session, the intensity of CL decreases significantly and the decaying of CL is governed by fast and slow time components. By comparing the temporal profile of FL to that of the corresponding CL, it is found that the slow component is mainly attributed to the probe pharmacokinetics, whereas the fast component is likely due to rapid oxygen consumption as a result of PDT treatment. With carefully selected criteria, it is possible to minimize the effect of probe pharmacokinetics. This significantly improves the monitoring method for practical applications.
Photodynamic therapy (PDT) is a cancer therapy most of which using light excites sensitizer mainly to produce singlet oxygen (1O2) to kill tumor cells by oxidation reaction. Monitoring the singlet oxygen production is an important task for getting more useful dosage information in photodynamic therapy to enhance the effect. In order to monitor singlet oxygen in PDT, the Chemiluminescence (CL) probe, which could react with singlet oxygen and emit photons, was selected and employed on mice to produce CL. The CL was collected and recorded by a single photon detection system in real time. The results showed that the signal intensity was high and indicated that the chemiluminescence could measure singlet oxygen in vivo sensitively. And during photodynamic therapy the CL signal dropped gradually. Different therapy dosages had different decay life. Any of the decay had two different parts: the rapid component and the slow component. During PDT, reactive oxygen would oxidize biomolecules of tissue, and oxygen was consumed. It would cause a rapid component; by combining with chemiluminescence and fluorescence detection technique, the first-order elimination coefficient of tissue was proved to be degressive during PDT. We deduced that the damaged vascular in PDT would provide littler oxygen and tissue hypoxia was more severely. It may quicken CL decay and caused the slow component. In conclusion, the results proved that monitoring 1O2 by CL could give useful information not only to evaluate the effect of PDT but also to judge the tissue oxygen depletion.
KEYWORDS: Photodynamic therapy, Skin, Oxygen, Luminescence, In vivo imaging, Chemiluminescence, Tissue optics, In situ metrology, Signal detection, Light scattering
Singlet oxygen (1O2) is an important factor mediating cell killing in photodynamic therapy (PDT). We previously reported that chemiluminescence (CL) can be used to detect 1O2 production in PDT and linked the signal to the PDT-induced cytotoxicity in vitro. We develop a new CL detection apparatus to achieve in vivo measurements. The system utilizes a time-delayed CL signal to overcome the interference from scattered excitation light, thus greatly improving the accuracy of the detection. The system is tested on healthy skin of BALB/ca mouse for its feasibility and reliability. The CL measurement is made during a synchronized gating period of the irradiation light. After each PDT treatment and in situ CL measurement, the skin response is scored over a period of 2 weeks. A remarkable relationship is observed between the score and the CL, regardless of the PDT treatment protocol. Although there are many issues yet to be addressed, our results clearly demonstrate the feasibility of CL measurement during PDT and its potential for in vivo PDT dosimetry. This requires further investigations.
Photodynamic therapy (PDT) is an important method to treat tumor. It is known that singlet oxygen (1O2) is the main
factor mediating cytotoxicity in PDT. The effectiveness of a PDT treatment is directly linked to the 1O2 produced in the
target. So to control the dose of 1O2 is very important. Although the luminescence from 1O2 can be detected and is
suggested as an indicator for evaluating photodynamic therapy, the inherited disadvantages limit its potential for in vivo
applications. We have previously reported that chemiluminescence (CL) can be used to detect 1O2 production in PDT and
linked the signal to the cytotoxicity, but the irradiation of laser decrease the sensitivity of the detection in vivo. During
PDT the high sensitivity probe, Fluoresceinyl Cypridina Luciferin Analog (FCLA), is used to monitor 1O2. In order to
avoid the infection of irradiation light, the delayed CL of FCLA is used to indicate 1O2. After recording the delayed CL
during PDT and scoring the skin of mice after PDT, the statistic analysis was done. The data shows a remarkable
relationship between the score and the CL. the result suggests that the CL can be used as a dose metric in vivo in PDT.
It is known that singlet oxygen (1O2) is the main factor mediating cytotoxicity in photodynamic therapy (PDT). The effectiveness of a PDT treatment is directly linked to the 1O2 produced in the target. Although the luminescence from 1O2 is suggested as an indicator for evaluating photodynamic therapy, the inherent disadvantages limit its potential for in vivo applications. We have previously reported that chemiluminescence can be used to detect 1O2 production in PDT and have linked the signal to the cytotoxicity. We further our investigation for monitoring 1O2 production during PDT. The lifetime of 3,7-dihydro-6-{4-[2-(N-(5-fluoresceinyl)thioureido)ethoxy]phenyl}-2-methylimidazo {1,2-a} pyrazin-3-one-chemiluminescence (FCLA-CL) is evaluated, and the results show that it is much longer than that of direct luminescence of 1O2. A gated measurement algorithm is developed to fully utilize the longer lifetime for a clean measurement of the CL without the interference from the irradiation light. The results show that it is practically feasible to use the technique to monitor the 1O2. Compared to the direct 1O2 luminescence measurement, our new technique is sensitive and can be realized with a conventional optical detector with excellent signal-to-noise ratio. It thus provides a means for real-time in vivo monitoring of 1O2 production during PDT.
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