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The morphological and hemodynamic characterization of the microvascular network around the gastrointestinal (GI) tract can be of significant clinical value for the early diagnosis and treatment of GI tract cancer. Ultrasound localization microscopy (ULM) imaging has been demonstrated to be capable of resolving the microvascular network. However, the endoscopic application of ULM imaging techniques is still unknown. In this study, an endoscopic ultrasound localization microscopy (e-ULM) imaging technique was developed to evaluate the changes of microvasculature during GI tract tumor growth.A customized circular array transducer (center frequency: 6.8 MHz) and the coherent diverging wave compounding method were used to generate B-mode images. Spatiotemporal singular value decomposition processing was used to eliminate the background signals before signal localizations. The centroids of spatially isolated signals were localized and summed to generate the final super-resolution image.The final microvasculature map of a rabbit GI tract tumor reveals that e-ULM can be used to surpass the diffraction limit in traditional endoscopic ultrasound (EUS) imaging. Furthermore, it is observed that data from different stages of tumor growth exhibit significant differences in microvascular pattern and density.Our study demonstrated the implementation and application of an in vivo e-ULM imaging technique for the evaluation of the microvasculature of GI tumors.The efficient e-ULM imaging technique shows potential for use in the detection of GI tract tumor microcirculation changes and subsequent diagnosis of GI tract cancer.

Objectives: The objective of this study was to demonstrate the feasibility of using noninvasive photoacoustic imaging technology along with novel semiconducting polymer nanoparticles for in vivo identifying inflammatory components in carotid atherosclerosis and assessing the severity of inflammation using mouse models. Methods and Results: Healthy carotid arteries and atherosclerotic carotid arteries were imaged in vivo by the noninvasive photoacoustic imaging system. Molecular probes PBD-CD36 were used to label the inflammatory cells to show the inflammation information by photoacoustic imaging. In in vivo imaging experiments, we observed the maximum photoacoustic signal enhancement of 4.3, 5.2, 8 and 16.3 times between 24 h post probe injection and that before probe injection in four carotid arteries belonging to three atherosclerotic mice models. In the corresponding carotid arteries stained with CD36, the ratio of 0.043, 0.061, 0.082 and 0.113 was found between CD36 positive (CD36(+)) expression area and intima-media area (P < 0.05). For the CD36(+) expression less than 0.008 in eight arteries, no photoacoustic signal enhancement was found due to the limited system sensitivity. The photoacoustic signal reflects CD36(+) expression in plaques, which shows the feasibility of using photoacoustic imaging for in vivo assessment of carotid atherosclerosis. Conclusion: This research demonstrates a semiconducting polymer nanoparticle along with photoacoustic technology for noninvasive imaging and assessment of inflammation of carotid atherosclerotic plaques in vivo.

Fluorescent carbon quantum dots (CQDs) are a new class of carbon nanomaterials that have excellent biocompatibility and low toxicity, useful for cell labeling and bioimaging. However, it is challenging to reproducibly create CQDs that are uniform and small in size with controlled toxicity and fluorescence properties, and this status quo hinders the practical application of CQDs, especially in vivo. In this report, CQDs with a uniform size of ∼1.53 ± 0.42 nm are synthesized via in situ pyrolysis of organics confined in the smallest-pore zeolite SAPO-20 with a micropore aperture of 0.28 nm. The ultrasmall fluorescent CQDs show a bright green fluorescence with a quantum yield (QY) of 16%, higher than that of most of the bare CQDs without any functionalization and maximum emission at 523 nm under the irradiation of xenon-light at an excitation wavelength of 470 nm. X-ray photoelectron spectroscopy (XPS) characterization confirms the presence of rich carboxyl and hydroxyl groups on the CQD surface containing N- and O-based functional groups. The synthesized CQDs with high QY and low cytotoxicity have been successfully used for cellular imaging with excellent biocompatibility.

Structural abnormalities and functional changes of renal microvascular networks play a significant pathophysiologic role in the occurrence of kidney diseases. Super-resolution ultrasound imaging has been successfully utilized to visualize the microvascular network and provide valuable diagnostic information. To prevent the burst of microbubbles, a lower mechanical index (MI) is generally used in ultrasound localization microscopy (ULM) imaging. However, high-noise levels lead to incorrect signal localizations in relatively low-MI settings and deep tissue. In this study, we implemented a block-matching threedimensional (BM3D) image-denoising method, after the application of singular value decomposition filtering, to further suppress the noise at various depths. The in vitro flow-phantom results show that the BM3D method helps the significant reduction of the error localizations, thus improving the localization accuracy. In vivo rhesus macaque experiments help conclude that the BM3D method improves the resolution more than other image-based denoising techniques, such as the nonlocal means method. The obtained clutter-filtered images with fewer incorrect localizations can enable robust ULM imaging, thus helping in establishing an effective diagnostic tool.

Intravascular photoacoustic (IVPA) imaging technology enables the visualization of pathological characteristics (such as inflammation activities, lipid deposition) of the artery wall. Blood flushing is a necessary step in improving the imaging quality in in vivo IVPA imaging. But the limited imaging speed of the systems stretches their flushing time, which is an important obstacle of their clinical translations. In this paper, we report an improvement in IVPA/IVUS imaging speed to 100 frames per second. The high-speed imaging is demonstrated in rabbit in vivo, visualizing the nanoparticles accumulated on abdominal aorta wall at the wavelength of 1064 nm, in real time display. Blood flushing in vivo improves the IVPA signal-noise-ratio by around 3.5 dB. This study offers a stable, efficient and easy-to-use tool for instantaneous disease visualization and disease diagnosis in research and forwards IVPA/IVUS imaging technology towards clinical translations.

Photodynamic therapy (PDT) is a non-invasive therapeutic strategy for cancer treatment but it always suffers from low reactive oxygen species (ROS) efficiency generated from traditional organic dyes owing to weak absorption in the optical transparent window of biological tissues and fluorescence quenching at a concentrated solution or in nanoparticles. Herein, we present cationic lipid-encapsulated aggregation-induced emission (AIE) nanoparticles (NPs) that have a high quantum yield (23%) and a maximum two-photon absorption (TPA) cross-section of 560 GM irradiated by near infrared light (800 nm). The AIE NPs can serve as imaging agents for spatiotemporal imaging of tumor tissues with a penetration depth up to 505 µm on mice melanoma model. Noteworthy, the AIE NPs can efficiently generate singlet oxygen (1O2) and highly toxic hydroxyl radicals (·OH) upon 800 nm-light irradiation for photodynamic tumor ablation. In addition, the AIE NPs can be effectively cleared from the mouse body after the imaging and therapy. This study provides a new strategy to develop theranostic agent for cancer image-guided PDT with high brightness, superior photostability and high biosafety

Fluorescence probes with aggregation-induced emission (AIE) characteristics are of great importance in biomedical imaging with superior spatial and temporal resolution. However, the lack of toxicity studies and deep tissue imaging in nonhuman primates hinders their clinical translation. Here, we report the blood chemistry and histological analysis in nonhuman primates treated with AIE probes over tenfold of an intravenous dose of clinically used indocyanine green (ICG) during a study period of 36 days to demonstrate AIE probes are nontoxic. Furthermore, through bright and nontoxic AIE probes and fluorescence imaging in the second window (NIR-II, 1,000–1,700 nm), we achieve an unprecedented 1.5-centimeter-deep vascular imaging in nonhuman primates, breaking the current limitation of millimeter-deep NIR-II fluorescence imaging. Our important findings, i.e., nontoxic features of AIE probes and centimeter-deep NIR-II vascular imaging in nonhuman primates, may facilitate successful translation of AIE probes in clinical trials.

Glioma is the most frequent primary brain tumour of the central nervous system. Its high aggressiveness and deep‐seated brain lesion make it a great challenge to develop a non‐invasive, precise and effective treatment approach. Here, we report a multifunctional theranostic agent that can integrate imaging and therapy into a single nano‐platform for imaging‐guided sonodynamic therapy (SDT). The SDT agents were fabricated by encapsulation of sinoporphyrin sodium (DVDMS) chelating with manganese ions into nanoliposomes (DVDMS‐Mn‐LPs). DVDMS‐Mn‐LPs are physiologically stable and biologically compatible, and they can produce singlet oxygen upon ultrasound irradiation to kill cancer cells. Both cell and animal studies demonstrated that SDT with DVDMS‐Mn‐LPs can significantly improve the antitumour growth efficiency even in the presence of skull. In addition, DVDMS‐Mn‐LPs are good for MR and fluorescence imaging. Thus, DVDMS‐Mn‐LPs reported here may provide a promising strategy for imaging‐guided modality for glioma treatment.

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS2–ICG hybrid with indocyanine green (ICG) conjugated to the surface of MoS2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS2–ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS2–ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine.

The visualization of the treatment process in situ could facilitate to accurately monitor cancer photothermal therapy (PTT), and dramatically decrease the risk of thermal damage to normal cells and tissues, which represents a major challenge for cancer precision therapy. Herein, we prepare theranostic nanoprobes (NPs) for Forster resonance energy transfer (FRET)-based dual-modal imaging-guided cancer PTT, and clear visualization of the therapeutic process. The FRET-based theranostic NPs exhibit high FRET efficiency (88.2%), good colloidal stability, and tumor-targeting ability. Tumor tissue and surrounding blood vessels are visualized clearly by FRET-based NIR fluorescence imaging with a high signal-to-background ratio (14.5) and photoacoustic imaging with an excellent resolution at 24 h post injection of NPs. Under the guidance of dual-modal imaging, the NPs-induced photothermal effect selectively destructs cancer cells, simultaneously decreasing the FRET efficiency and leading to fluorescence and photoacoustic signal changes. The sensitive self-feedback process enables the in situ visualization of therapeutic process and precision guidance of in vivo cancer PTT. A high therapeutic efficacy and minimum side effects are achieved in C6 tumor-bearing nude mice, holding great promise for precision therapy and cancer theranostics.

Glioblastoma multiforme (GBM) diffusely infiltrates normal brain tissue. The presence of the blood-brain barrier (BBB) poses difficulties for targeted delivery of currently available antitumor drugs. Novel brain drug delivery strategies are far from satisfactory for glioma treatment. Recently, focused ultrasound (FUS) combined with microbubbles presents a transient, reversible, and noninvasive approach for local induction of BBB opening. This strategy demonstrated its potential to increase local concentrations of both diagnostic and therapeutic agents in glioma therapy. Current status and related physic mechanisms of this drug delivery technique are discussed in this review. Delivery efficiency enhancement in many preclinical glioma models was obtained by FUS-BBB opening combined with various nanoparticles. And, the clinical translational status of FUS-BBB will be discussed.

Background: Engineering a single organic-molecule-based nanoparticle integrating precise diagnosis and effective therapy is of great significance for cancer treatment and future clinical applications but remains a great challenge. The goal of this study is to explore small organic molecule-based nanoparticles with high photothermal conversion efficiency for photoacoustic imaging-guided therapy. Methods: Heptacyclic B, O-chelated BODIPY structure (namely Boca-BODIPY) with strong near-infrared (NIR) absorption was designed as a theranostic agent through simply molecular engineering, in which heavy atoms and alkyl chains were introduced to promote its application for tumor theranostics. The Boca-BODIPY molecules are further encapsulated in reduced bovine serum albumin (BSA) through self-assembly. Results: The BSA-Boca-BODIPY exhibited excellent biocompatibility, extraordinary stability and high photothermal conversion efficiency up to 58.7%. The nanoparticles could dramatically enhance photoacoustic contrast of the tumor region, and the signal-to-noise ratio was increased about 14 times at 10 h post intravenous injection in 4T1 tumor-bearing mice. In addition, the nanoassemblies can efficiently convert laser energy (808 nm, 0.75 w cm-2, 5min) into hyperthermia for tumor ablation. Under the photoacoustic imaging-guided photothermal therapy (PTT), the 4T1 cancer cells were efficiently killed, no tumor recurrence and PTT-induced toxicity is observed. Conclusions: Molecular engineering is a promising way to design organic-molecule-based nanoparticles for cancer theranostics. Other organic-molecule-based nanoparticles which show great promise for imaging-guided cancer precision therapy can be engineered through this method.

Correction for ‘Highly penetrative liposome nanomedicine generated by a biomimetic strategy for enhanced cancer chemotherapy’ by Yali Jia et al., Biomater. Sci., 2018, 6, 1546–1555, DOI: 10.1039/C8BM00256H.

Photodynamic therapy (PDT) is a noninvasive and effective approach for cancer treatment. The main bottlenecks of clinical PDT are poor selectivity of photosensitizer and inadequate oxygen supply resulting in serious side effects and low therapeutic efficiency. Herein, a thermal-modulated reactive oxygen species (ROS) strategy using activatable human serum albumin-chlorin e6 nanoassemblies (HSA-Ce6 NAs) for promoting PDT against cancer is developed. Through intermolecular disulfide bond crosslinking and hydrophobic interaction, Ce6 photosensitizer is effectively loaded into the HSA NAs, and the obtained HSA-Ce6 NAs exhibit excellent reduction response, as well as enhanced tumor accumulation and retention. By the precision control of the overall body temperature instead of local tumor temperature increasing from 37 °C to 43 °C, the photosensitization reaction rate of HSA-Ce6 NAs increases 20%, and the oxygen saturation of tumor tissue raise 52%, significantly enhancing the generation of ROS for promoting PDT. Meanwhile, the intrinsic fluorescence and photoacoustic properties, and the chelating characteristic of porphyrin ring can endow the HSA-Ce6 NAs with fluorescence, photoacoustic and magnetic resonance triple-modal imaging functions. Upon irradiation of low-energy near-infrared laser, the tumors are completely suppressed without tumor recurrence and therapy-induced side effects. The robust thermal-modulated ROS strategy combined with albumin-based activatable nanophotosensitizer is highly potential for multi-modal imaging-guided PDT and clinical translation.

Multidrug-resistant Staphylococcus aureus (MRSA) seriously endanger human health. The development of efficient methods to eliminate the infections and monitor the treatment process are of great significance. Near-infrared-II (NIR-II) photoacoustic (PA) imaging and photothermal therapy (PTT) are highly integrated theranostic platforms with superior performance including a low imaging background, increased tissue penetration depth, and high photothermal threshold. Herein, we report an activatable near-infrared II (NIR-II) phototheranostic strategy using miniature Au/Ag nanorods (NRs) for the photochemical synergistic therapy of MRSA infections and in situ monitoring of the treatment progress. Au/Ag NRs were efficiently activated by ferricyanide solution and allowed to continuously release free Ag+ to eliminate MRSA, triggering NIR-II photothermal and PA performance enhancement. The activated NIR-II photothermal effect in turn accelerated the release of free Ag+ from Au/Ag NRs for the synergistic elimination of gram-positive Staphylococcus aureus and promoted wound healing. No photothermal damages or free Ag+-induced side effects were observed in treated mice. After synergistic treatment, a 20-fold NIR-II PA signal increase with a maximum signal-to-noise measurement of 9.5 was observed between the implanted site and normal tissue, enabling sensitive monitoring of Ag+ release process. The prepared Au/Ag NRs were stable and biocompatible, showing great potential for activatable NIR-II phototheranostic application.

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS2–ICG hybrid with indocyanine green (ICG) conjugated to the surface of MoS2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS2–ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS2–ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine. Electronic supplementary material The online version of this article (10.1007/s40820-018-0202-8) contains supplementary material, which is available to authorized users.

The visualization of the treatment process in situ could facilitate to accurately monitor cancer photothermal therapy (PTT), and dramatically decrease the risk of thermal damage to normal cells and tissues, which represents a major challenge for cancer precision therapy. Herein, we prepare theranostic nanoprobes (NPs) for Förster resonance energy transfer (FRET)-based dual-modal imaging-guided cancer PTT, and clear visualization of the therapeutic process. The FRET-based theranostic NPs exhibit high FRET efficiency (88.2%), good colloidal stability, and tumor-targeting ability. Tumor tissue and surrounding blood vessels are visualized clearly by FRET-based NIR fluorescence imaging with a high signal-to-background ratio (14.5) and photoacoustic imaging with an excellent resolution at 24 h post injection of NPs. Under the guidance of dual-modal imaging, the NPs-induced photothermal effect selectively destructs cancer cells, simultaneously decreasing the FRET efficiency and leading to fluorescence and photoacoustic signal changes. The sensitive self-feedback process enables the in situ visualization of therapeutic process and precision guidance of in vivo cancer PTT. A high therapeutic efficacy and minimum side effects are achieved in C6 tumor-bearing nude mice, holding great promise for precision therapy and cancer theranostics.

Nanoprobes with enzyme-like properties attracted a growing interest in early screening and diagnosis of cancer. To achieve high accuracy and specificity of tumor detection, the design and preparation of enzyme mimetic nanoprobes with high enzyme activity, tumor targeting and excellent luminescence property is highly desirable. Herein, we described a novel kind of fluorescence enzyme mimetic nanoprobe based on folate receptor-targeting Au nanoclusters. The nanoprobes exhibited excellent stability, low cytotoxicity, high fluorescence and enzyme activity. We demonstrated that the nanoprobes could be used for tumor tissues fluorescence/visualizing detection. For the same tumor tissue slice, the nanoprobes peroxidase staining and fluorescent staining were obtained simultaneously, and the results were mutually complementary. Therefore, the fluorescence enzyme mimetic nanoprobes could provide a molecular colocalization diagnosis strategy, efficiently avoid false-positive and false-negative results, and further improve the accuracy and specificity of cancer diagnoses. By examining different clinical samples, we demonstrated that the nanoprobes could distinguish efficiently cancerous cells from normal cells, and exhibit a clinical potential for cancer diagnosis.

Photoacoustic (PA) imaging and photothermal therapy (PTT) as light-induced theranostic platforms have been attracted much attention in recent years. However, the development of highly efficient and integrated phototheranostic nanoagents for amplifying PA imaging and PTT treatments poses great challenges. Here, we report a novel phototheranostic nanoagent using indocyanine green-loaded polydopamine-reduced graphene oxide nanocomposites (ICG-PDA-rGO) with amplifying PA and PTT effects for cancer theranostics. The results demonstrate that the PDA layer coating on the surface of rGO could effectively absorb a large number of ICG molecules, quench ICG's fluorescence, and enhance the PDA-rGO's optical absorption at 780 nm. The obtained ICG-PDA-rGO exhibits stronger PTT effect and higher PA contrast than that of pure GO and PDA-rGO. After PA imaging-guided PTT treatments, the tumors in 4T1 breast subcutaneous and orthotopic mice models are suppressed completely and no treatment-induced toxicity being observed. It illustrates that the ICG-PDA-rGO nanocomposites constitute a new class of theranostic nanomedicine for amplifying PA imaging and PTT treatments.

The blood brain barrier is the main obstacle to delivering diagnostic and therapeutic agents to the diseased sites of brain. It is still of great challenge for the combined use of focused ultrasound (FUS) and theranostic nanotechnology to achieve noninvasive and localized delivery of chemotherapeutic drugs into orthotopic brain tumor. In this work, a unique theranostic nanoplatform for highly efficient photoacoustic imaging‐guided chemotherapy of brain tumor both in vitro and in vivo, which is based on the utilization of hollow mesoporous organosilica nanoparticles (HMONs) to integrate ultrasmall Cu2− xSe particles on the surface and doxorubicin inside the hollow interior, is synthesized. The developed multifunctional theranostic nanosystems exhibit tumor‐triggered programmed destruction due to the reducing microenvironment‐responsive cleavage of disulfide bonds that are incorporated into the framework of HMONs and linked between HMONs and Cu2− xSe, resulting in tumor‐specific biodegradation and on‐demand drug‐releasing behavior. Such tumor microenvironment‐responsive biodegradable and biocompatible theranostic nanosystems in combination with FUS provide a promising delivery nanoplatform with high performance for orthotopic brain tumor imaging and therapy.

The interaction of water-soluble CdSe quantum dots (QDs) with gold (Au) nanoparticles was investigated by ultraviolet visible absorption spectroscopy. The results showed that the aggregation of Au nanoparticles was induced by CdSe QDs. The influences of factors such as the size of Au nanoparticles, acidity, buffer concentration and the concentration ratio of the CdSe QDs to Au nanoparticles were each investigated. The comparison of two different particle sizes (16 and 25 nm) of Au nanoparticles that interact with CdSe QDs in the solution showed that the aggregation of small Au nanoparticles (16 nm) is easier than that of big Au nanoparticles (25 nm). At pH 7.0 phosphate buffer solution (0.02 M), the optimal molar ratio of CdSe:Au is about 3100:1 according to calculations.

Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

A key challenge to strengthen anti-tumor efficacy is to improve drug accumulation in tumors through size control. To explore the biodistribution and tumor accumulation of nanoparticles, we developed indocyanine green (ICG) loaded poly (lactic-co-glycolic acid) (PLGA) -lecithin-polyethylene glycol (PEG) core-shell nanoparticles (INPs) with 39 nm, 68 nm and 116 nm via single-step nanoprecipitation. These INPs exhibited good monodispersity, excellent fluorescence and size stability, and enhanced temperature response after laser irradiation. Through cell uptake and photothermal efficiency in vitro, we demonstrated that 39 nm INPs were more easily be absorbed by pancreatic carcinoma tumor cells (BxPC-3) and showed better photothermal damage than that of 68 nm and 116 nm size of INPs. Simultaneously, the fluorescence of INPs offered a real-time imaging monitor for subcellular locating and in vivo metabolic distribution. Near-infrared imaging in vivo and photothermal therapy illustrated that 68 nm INPs showed the strongest efficiency to suppress tumor growth due to abundant accumulation in BxPC-3 xenograft tumor model. The findings revealed that a nontoxic, size-dependent, theranostic INPs model was built for in vivo cancer imaging and photothermal therapy without adverse effect.

Aptamers have emerged as promising molecular probes for cancer diagnosis. However, their application for in vivo cancer imaging remains limitation due to the poor stability in blood and the degradation by nucleases. In the present study, we generated PEI/aptamer molecular complexes for cancer imaging in vivo by using deoxyribonuclease (DNase)-activatable fluorescence probes (DFProbes) to monitor DNA degradation. The results showed that the complexes with PEI at the N/P ratio from 3.8 to 15 effectively prevented the degradation of DFProbes both in vitro and in vivo. Moreover, PEI successfully protected TD05 aptamers from DNase degradation without affecting its specific recognition of Ramos cells. In tumor bearing mice, PEI/aptamer molecular complexes further demonstrated superior passive tumor targeting and extended circulation time as compared with free aptamer. Hence, the well-defined PEI/aptamer probe is a novel strategy to deliver targeted aptamer for tumor diagnosis and imaging in vivo.

Indocyanine green (ICG) is a near-infrared (NIR) fluorescence dye for extensive biological application, but limited by its poor aqueous stability in vitro, concentration-dependent aggregation, rapid elimination from the body, and lack of target specificity. In this paper, to overcome these limitations, folate receptor-targeted, ICG dye-doped poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) were constructed by a single-step self-assemble and nanoprecipitation method. The prepared FA-ICG-PLGA-lipid NPs exhibited good biocompatibility, monodispersity, excellent NIR penetration ability, significant stability against photobleaching and long circulation time. The intracellular uptake experiment proved the targeting efficacy of the FA-ICG-PLGA-lipid NPs was more effective in folate receptor over-expressing MCF-7 cells than folate receptor negative A549 cells. Furthermore, the in vivo experiments showed the FA-ICG-PLGA-lipid NPs were specifically targeted to the tumor, and its circulation time was much longer than free ICG. These biocompatible and biodegradable NIR-NPs prove a potential application in tumor diagnosis and targeted imaging due to its high aqueous stability, excellent NIR optical properties and significantly targeting property in vivo.

A novel method for the detection of hydrogen peroxide (H(2)O(2)) has been developed, based on electrogenerated chemiluminescence (ECL) of blue emitting ZnSe quantum dots (QDs) in aqueous solution. The weak ECL emission of ZnSe QDs was generated when the electrode potential was scanned from 0.0 to -1.4V (versus Ag/AgCl), and the ECL intensity was greatly enhanced in the presence of H(2)O(2) or dissolved oxygen. Under the optimal conditions, the dynamic range is from 6.10 x 10(-7) to 3.10 x 10(-4)M H(2)O(2), and the detection limit (at S/N=3) is 2.00 x 10(-7)M. The relative standard deviation (at 5.00 x 10(-5)M of H(2)O(2)) is 2.70% (n=11). A possible reaction mechanism of ECL of ZnSe QDs was also investigated. As a novel biosensor, it was used to detect H(2)O(2) in the pig kidney (pk-15) cell, vero cell and mineral water, respectively. Moreover, the proposed biosensor showed a good reproducibility and potential application in real samples.

The effect of $\mathrm{Cu}$-doping at $\mathrm{Mn}$-site on structural, magnetic and transport properties in electron-doped manganites ${\mathrm{La}}_{0.85}{\mathrm{Te}}_{0.15}{\mathrm{Mn}}_{1\ensuremath{-}x}{\mathrm{Cu}}_{x}{\mathrm{O}}_{3}$ $(0\ensuremath{\leqslant}x\ensuremath{\leqslant}0.20)$ has been investigated. Based on the analysis of structural parameter variations, the valence state of the $\mathrm{Cu}$ ion in $\mathrm{Cu}$-doped manganites is suggested to be $+2$. All samples undergo the paramagnetic-ferromagnetic (PM-FM) phase transition. The Curie temperature ${T}_{c}$ decreases and the transition becomes broader with increasing $\mathrm{Cu}$-doping level, in contrast, the magnetization magnitude of $\mathrm{Cu}$-doping samples at low temperatures increase as $x\ensuremath{\leqslant}0.15$. The insulator-metal (I-M) transition moves to lower temperatures with increasing $\mathrm{Cu}$-doping content and disappears as $xg0.1$. In addition, the higher temperature resistivity $\ensuremath{\rho}$ peak in double-peak-like $\ensuremath{\rho}(T)$ curves observed in no $\mathrm{Cu}$-doping sample is completely suppressed as $\mathrm{Cu}$-doping level $x=0.1$ and $\ensuremath{\rho}(T)$ curve only shows single I-M transition at the low temperature well below ${T}_{C}$. The results are discussed according to the change of magnetic exchange interaction caused by $\mathrm{Cu}$-doping.

The effect of grain size on structural, magnetic and transport properties in electron-doped manganites La0.9Te0.1MnO3 has been investigated. All samples show a rhombohedral structure with the space group at room temperature. It shows that the Mn-O-Mn bond angle decreases and the Mn-O bond length increases with the increase of grain size. All samples undergo paramagnetic (PM)-ferromagnetic (FM) phase transition and an interesting phenomenon that both magnetization and the Curie temperature decrease with increasing grain size is observed, which is suggested to mainly originate from the increase of the Mn-O bond length . Additionally, obviously increases with decreasing grain size due to the increase of both the height and width of tunneling barriers with decreasing the grain size. The results indicate that both the intrinsic colossal magnetoresistance (CMR) and the extrinsic the extrinsic interfacial magnetoresistance (IMR) can be effectively tuned in La0.9Te0.1MnO3 by changing grain size., 15 pages,4 figures. Solid state communications 132(2004)83-87