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Finding an effective monitoring and evaluation factor for therapeutic effect of microwave ablation is becoming a research focus. Previous MWA experiments on in vitro porcine liver found that reduced scattering coefficient ( μ's ) is an efficient optical evaluation parameter. Results indicated that μ's of normal tissue and coagulation tissue is 3-5 cm-1 and 17-19 cm-1, respectively, and μ's is highly related to the degree of thermal damage. This paper aims to validate if these results from in vitro porcine liver also applies to real tumor. Two sets of experiments were carried out with human liver tumor specimens. In the first experimental set, the tumor specimen was heated by water bath at constant temperature of 80 ℃ for 5 minutes, and μ's was obtained before and after the heating process. In the second set, another tumor specimen was heated by MWA with microwave power of 10 W for 5 min, reduced scattering coefficient and temperature changes were measured during ablation. In the first experiment, μ's value was 4.10 cm-1 before heating and increased to 17.16 cm- 1 after complete tissue protein coagulation. In the second experiment, μ's grew exponentially first and eventually stabilized. μ's values are consistent with previous experiments on in vitro porcine liver. These results also validates that the μ's values reflect the degree of thermal damage, and be captured in real-time. To sum up, μ's is an effective real-time thermal damage monitoring and evaluation factor that can be applied to real tumors.

In the clinical treatment of tumors using microwave ablation (MWA), although temperature can be used as an important reference index for evaluating the curative effect of MWA, it cannot fully reflect the biological activity status of tumor tissue during MWA. Finding multi-parameter comprehensive evaluation factors to achieve real-time evaluation of therapeutic effects has become the key for precise ablation. The near-infrared spectroscopy and optical parameters (absorption coefficient (μα), reduced scattering coefficient (μ's), etc.) of biological tissues also change dynamically due to changes in cell morphology and protein tertiary structure during tissue thermal damage. Real-time measurement of the optical parameters of tumor during MWA can be achieved by using minimally invasive function near-infrared spectroscopy. MWA of tumor is essentially a process of protein denaturation and gradual coagulation. During the process of coagulation, the tissue hardness (which could be reflected by Young's modulus, E) also changes in real time. Shear wave elastography can measure Young's modulus in real-time and obtain 2D image. This paper focuses on the real-time evaluation of MWA based on reduced scattering coefficient and Young's modulus. The MWA experiment was conducted on porcine liver in vitro, the two-parameter simultaneous acquisition system was designed to obtain the μ's and E of the liver during MWA. After measuring the μ's and E of different zones after ablation, combining the parameter changes during the ablation and the analysis of the cell activity of the liver after ablation, an evaluation model was established.

Integrin α5β1 is a widely-recognized target for molecular probes in various pathological conditions, especially cancer. The development of computer screening approaches to identify novel high affinity ligands to tumor markers has paved the way for a new generation of tumor identification technology. In this study, we have developed an efficient pharmacophore-based computational strategy to screen two novel peptides, RYr and H5, with high affinity to integrin α5β1. Noninvasive optical imaging data showed that these two peptides could be specifically uptaken by α5β1 overexpressed-tumor cells in vitro and in vivo. And these peptides-based probes could retain in tumor tissue for precise tumor identification. Results indicated that the newly identified peptides with high affinity to integrin α5β1 can be used for precise tumor identification and treatment. And this work exploited more functionalities of pharmacophore-based computational strategy for screening targeting-peptides.

MicroRNAs (miRNAs) play important roles in a wide range of biological processes, including proliferation, development, metabolism, immunological response, tumorigenesis, and viral infection. The detection of miRNAs is imperative for gaining a better understanding of the functions of these biomolecules and has great potential for the early diagnosis of human disease as well as the discovery of new drugs through the use of miRNAs as targets. In this article, we develop a highly sensitive, and specific miRNA assay based on the two-stage isothermal amplification reactions and molecular beacon. The two-stage isothermal amplification reactions involves two templates and two-stage amplification reactions under isothermal conditions. The first template enables the amplification of miRNA, and the second template enables the conversion of miRNA to the reporter oligonucleotide(Y). Importantly, different miRNAs can be converted to the same Y seperately, which can hybridize with the same set of molecular beacon to generate fluorescent signals. This assay is highly sensitive and specific with a detection limit of 1 fM and can even discriminate single-nucleotide differences. Moreover, in combination with the specific templates, this method can be applied for multiplex miRNA assay by simply using the same molecular beacon. This method has potential to become a promising miRNA quantification method in biomedical research and clinical diagnosis.

Hepatocellular carcinoma (HCC) has been the third most common cause of cancer-related death worldwide. Glypican-3 (GPC3) is a heparin sulfate proteoglycan linked to the cell membrane by a glycosyl-phosphatidylinositol anchor (GPI) and is expressed by 75% of all hepatocellular carcinomas but undetectable in healthy liver tissue or liver with focal lesions. What’s more, GPC3 has been gradually applied in clinical applications as a specific indicator for the early detection and prognosis of HCC. As GPC3 can also regulate many pathways in HCC pathogenesis including Wnt, Hh and Yap signaling, it has been shown that GPC3 knockdown can inhibit HCC growth, reinforcing the important roles of GPC3 in HCC development. For HCC early detection, we designed a peptide targeting GPC3 that allows to establish a fluorescent dyes-labeled probe. Firstly, according to the structure of the GPC3 antibody GC33 and the positive peptide reported in the literature, we generated a peptide consisting of twelve amino acids named 12P that may bind to GPC3 with tight binding ability and specificity. In vitro testing, we utilized FCM and laser confocal microscopy to verify its specificity of targeting to the high expression cells of GPC3. What’s more, we linked 12P with a near infrared dye to verify its in vivo targeting ability. All results indicated that 12P possessed potent binding capacity which could be used as a targeting module in GPC3 detection probe.

MDR1 (multidrug resistance geneⅠ) mRNA expression is a promising biomarker for the prediction of doxorubicin resistance in clinic. However, the traditional technical process in clinic is complicated and cannot perform the real-time detection mRNA in living single cells. In this study, the expression of MDR1 mRNA was analyzed based on optimized gold nanoparticle beacon in tumor cells. Firstly, gold nanoparticle (AuNP) was modified by thiol-PEG, and the MDR1 beacon sequence was screened and optimized using a BLAST bioinformatics strategy. Then, optimized MDR1 molecular beacons were characterized by transmission electron microscope, UV–vis and fluorescence spectroscopies. The cytotoxicity of MDR1 molecular beacon on L-02, K562 and K562/Adr cells were investigated by MTT assay, suggesting that MDR1 molecular beacon was low inherent cytotoxicity. Dark field microscope was used to investigate the cellular uptake of hDAuNP beacon assisted with ultrasound. Finally, laser scanning confocal microscope images showed that there was a significant difference in MDR1 mRNA expression in K562 and K562/Adr cells, which was consistent with the results of q-PCR measurement. In summary, optimized MDR1 molecular beacon designed in this study is a reliable strategy for detection MDR1 mRNA expression in living tumor cells, and will be a promising strategy for in guiding patient treatment and management in individualized medication.

Early diagnosis and effective treatment of bacterial infection has become increasingly important. Herein, we developed a fluorescent nano-probe MPA@ZnO-PEP by conjugating SiO2-stabilized ZnO quantum dot (ZnO@SiO2) with bacteria-targeting peptide PEP, which was encapsulated with MPA, a near infrared (NIR) dye. The nanoprobe MPA@ZnO-PEP showed excellent fluorescence property and could specifically distinguish bacterial infection from sterile inflammation both in vitro and in vivo. The favorable biocompatability of MPA@ZnO-PEP was verified by MTT assay. This probe was further modified with antibiotic methicillin to form the theranostic nanoparticle MPA/Met@ZnO-PEP with amplified antibacterial activity. These results promised the great potential of MPA@ZnO-PEP for efficient non-invasive early diagnosis of bacterial infections and effective bacterial-targeting therapy.

In this study, we have prepared tumor-targeted hydrophilic UCNPs by coating folate-modified amphiphilic SOC polymer on the surface of OA-UNCPs through hydrophobic interaction. The produced FASOC-UCNPs have excellent optical properties and good dispersibility in aqueous solution. TEM image and FTIR spectra confirm the successful surface modification of OA-UCNPs and folate-conjugation on the UCNPs. Folate-conjugated UCNPs possess active-targeting ability mediated by FR, compared with passive-targeted SOC-UCNP taken up by tumors via the EPR effect. Singlet oxygen production in cancer cells induced by FASOC-UCNP-ZnPc demonstrates the great potential of the nanocomplex as a novel PDT agent based on UCNPs.

Docosahexaenoic acid(DHA) is an omega-3 C22 natural fatty acid with six cis double bonds and as a constituent of membranes used as a precursor for metabolic and biochemical path ways. In this manuscript,we describe the synthesis of near-infrared(NIR) flourescence ICG-Der-01 labeled DHA for in vitro and vivo tumor targeting.The structure of the probe was intensively characterized by UV and MS. The in vitro and vivo tumor targeting abilities of the DHA-based NIR probes were investigeted in MCF-7 cells and MCF-7 xenograft mice model differently by confocal microscopy and CCD camera. The cell cytotoxicity were tested in tumor cells MCF-7 .The results shows that the DHA-based NIR probes have high affinity with the tumor both in vitro and vivo.In addition ,we also found that the DHA-based NIR probes have the apparent cytotoxicity on MCF-7 cells .which demonstrated that DHA was conjugated with other antitumor drug could increase the abilities of antirumor efficacy .So DHA-ICG-Der-01 is a promising optical agent for diagnosis of tumors especially in their early stage.

In this manuscript, a new near-infrared (NIR) light-breakable amphiphilic block copolymer containing light-sensitive triggering group on the hydrophobic block was developed. By encapsulating NIR dye cypate inside micelles of poly (N-succinyl-N'-4- (2-nitrobenzyloxy)-succinyl chitosan) and exposing the micellar solution to 765.9 nm light, th e photo-cleavage reaction was activated and leading to the dissociation of micelles and release of co-loaded hydrophobic species. The UV-vis absorption spectra, fourier transform infrared (FTIR) spectra and 1 H nuclear magnetic resonance (H NMR) spectra of micelles were characteri zed. Triggered burst release of the payload upon NIR irradiation and subsequent degradation of the micelles were observed by transmission electron microscopy (TEM). This system represents a general and efficient method to circumvent the need for UV or visible light excitation that is a common drawback for light-responsive polymeric systems developed for potential biomedical applications. Key words : NIR light; controlled release; drug delivery; micelles 1. Introduction During the past decades, most functional micelles have found extensive use in drug delivery for their ability to encapsulate and retain hydrophobic drugs in their self-assembled interior [1]. In this regard, polymer micelles that are responsive to envi ronmental changes, such as pH [2] and temperature [3], or can be disrupted by external stimuli [4] ar e desirable. There has recently been growing interest in light-responsive micelles which can be disrupted by illumination. In order to make light-sensitive micelles, the main established approach is to incorporate photochromic groups onto the hydrophobic block of a micelle, whose photoreaction can increase the polarity of the block and thus shifts the hydrophilic-hydrophobic balance to render association of block polymer chains thermodynamically unstable [5]. o-nitrobenzyl moieties is a good candidate as the photochromic group in this approach since they can be triggered by one- and two-photo inducted absorption [6].

A system based on near-infrared light intensity was used to monitor mouse model of traumatic brain injury (TBI) noninvasively. The measurement system was controlled by microcontroller. Light from a 760/850nm dual-wavelength light emitting diode was coupled to a 0.6-mm-diameter optical fiber. The collection fibers were coupled to optoelectronic detectors, which were placed in the different distance from the source fiber. The system consisted of a constant current bias, a circuit lock-in amplifier (including band pass filter, lock-in amplifier, and low pass filter), a PCI 6240 data acquisition card and a multi-core-processor computer. The modified Lambert Beer law was used to calculate the concentration of ΔHbO2 and ΔHb. The sensitivity matrix was defined to evaluate the region of effective detection of optical probe. Five groups of TBI mouse models were built by Feeney's free-falling method. The data measured by system show after TBI the concentration of ΔHbO2 decreased and that of ΔHb increased. It can be concluded that the system can be used to monitor the changes of TBI of mouse non-invasively.

Signal transducer and activator of transcription (STAT) 5b is an important protein in JAK-STAT signal pathway and is responsible for the metastasis and proliferation of tumor cells. The determination of the STAT5b expression provides a way to study the mechanism of tumor progress. In this study, gold nanoparticles with different diameters were conjugated to the fluorescein modified STAT5b specific DNA sequence to form the beacon. The procedures for the beacon with better fluorescence properties were optimized. The fluorescence quenching and the recovery properties after hybridizing with mRNA of STAT5b were intensively investigated. Results indicate the gold nanoparticle based beacon is an effective probe for the determination of STAT5b protein expression in JAK-STAT signal pathway and has great potential in the study of drug screening and discovery.

The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to construct and evaluate the folate-decorated, self-assembled nanoparticles as candidates to deliver near infrared fluorescent dyes into tumors and to investigate the mechanisms underlying the tumor targeting with folate-decorated, self-assembled nanoparticles. Folate-decorated N-succinyl-N'-octyl chitosan (folate-SOC) were synthesized. The chemical modification chitosan could self-assemble into stable micelles in aqueous medium. Micelle size determined by size analysis was around 140 nm in a phosphate-buffered saline (PBS, PH 7.4). Folate-SOC could maintain their structure for up to 15 days in PBS. Near infrared dye ICG-Der-01 as a mode drug was loaded in the micelles, and the entrapment efficiency (EE) and drug loading (DL) were investigated. The targeted behavior of folate-SOC was evaluated by near-infrared fluorescence imaging in vivo on different groups of denuded mice, with A549 or Bel-7402 tumors. The optical imaging results indicated that folated-decorated SOC showed an excellent tumor specificity in Bel-7402 tumor-bearing mice, and weak tumor specificity in A549 tumor bearing mice. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.

Near infrared spectroscopy possess great potential for in vivo quantitative monitoring of drugs in animal subject. The accuracy of the measurements by near infrared technique should be evaluated by an established method. In this study, a near infrared fluorescence dye, cypate and its conjugation cypate-PEG were used as model drug for in vivo dynamic study. The pharmacokinetics of the model drug in mice subjects were investigated by near infrared spectroscopy and high performance liquid chromatography, respectively. The results from the two techniques were compared. The pharmacokinetic parameters calculated based on the acquired data by DAS software showed that there were no statistical differences between the two methods. The dynamic distribution of the model drugs in mouse model imaged by NIR image system indicated that cypate firstly accumulated in liver and was cleared from the enteron system, while cypate - PEG clearance from the urine system. Results indicated that NIR monitoring technique provide a promising quantitative way for in vivo monitoring the dynamics of drugs in animal subjects.

Near-infrared (NIR) fluorescence imaging possesses many advantages as an in vivo non-invasive optical imaging modality for studying diseases in preclinical models. In this study, low density lipoprotein(LDL) fraction was quickly isolated from human plasma by modified heparin-citrate precipitation method and then conjugated to near infrared fluorescence dye ICG-Der-02 with excitation and emission wavelengths at 760nm and 830nm, respectively. The conjugates LDL-ICG-Der-02 were intravenously injected into the mice bearing different tumor models. And real time series fluorescence tumor images at different intervals of post-injection were in vivo acquired by a self-built NIR reflectance fluorescence imaging system. Results demonstrated that LDL-ICG-Der-02 conjugates could efficiently target to the tumor sites that over-expressed LDL receptors and could be completely eliminated at last.

Nanoparticles have a promising application prospect in biomedical field. The study of their dynamic characteristics including in vivo distribution and clearance has the most important significance on their biological application. In this paper, bio-distribution and clearance of solid and colloid nanoparticles with different size in mouse model was intensively studied in vivo by using near infrared optical imaging technique. Here, nanohydrogels were synthesized by precipitation polymerization method and the size of the nanohydrogel could be arbitrarily manipulated according to different surfactant concentration. Near infrared fluorescence dye were entrapped into their inner core for in vivo studies. Meanwhile, the size of CdHgTe/SiO2 solid nanoparticles could be controlled by the thickness of SiO2 coated on the surface of CdHgTe. The results from the near infrared imaging showed that nanohydrogels with different size have the similar tissue distribution but CdHgTe/SiO2 nanoparticles in different size have a size-dependent organ specification. These results provided an important reference for the design of targeted drug delivery systems and their biomedical applications.

A new image reconstruction approach to optical computed tomography is proposed in which a BP neural network is used to express the nonlinear relation between the change of optical properties inside the biology tissue and photons distributing change around the surface. A modeling and simulation tool named Femlab and finite element method has been tested wherein the forward model on a basis of the diffusion equation. Based on the forward problem, a BP neural network was established to solve the inverse problem. Thus, the position and its corresponding optical properties of tissue change could be recognized by the network. New approach was suitable for clinical application for its fast reconstruct characteristic.

This paper reports authors' works on design of an optical fiber sensor which can in situ monitor and analyze the concentration and composition of pharmaceutical in blood. An optical probe is inserted in blood vessels, ultraviolet light is coupled into one branch of Y-type optical fiber to induce fluorescence emitting from the pharmaceutical in blood. The fluorescence is collected by another branch of Y optical fiber and detected by photomultiplier. The detected signal is sampled into computer which can process the data in realtime and display dynamically the fluorescence spectrum on the screen. Compared with ordinary analytical instruments such as various spectrometer and chromatographs, this sensor has the advantages that it can measure in situ and thus omit the process of extracting serum or plasma from blood and reduce the detecting time. This advantage has practical value in clinical diagnosis. In this research, the major difficulty is that the blood is not transparent. Authors apply a membrane adhered to the top of the probe and frustrating the access of hemocytes thus the fluorescence can be collected. This sensor can measure the concentration of pharmaceutical in blood in the grade of micrograms/milliliter.