Yigong Powder regulates CXCL12/CXCR4 signaling to reduce glutamate release and prevent cognitive decline in mouse model of aging / 中国中药杂志

This study aims to explore the effect of preventive administration of Yigong Powder on the learning and memory abilities of the mouse model of aging induced by D-galactose and decipher the underlying mechanism, so as to provide a basis for the application of Yigong Powder in the prevention and treatment of cognitive decline. Forty KM mice were randomized into control, model, donepezil(1.5 mg·kg~(-1)), and high-dose(7.5 g·kg~(-1)) and low-dose(3.75 g·kg~(-1)) Yigong Powder groups. The mice in other groups except the control group were injected with D-galactose(200 g·kg~(-1)) at the back of the neck for the modeling of aging. At the same time, the mice were administrated with corresponding drugs by gavage for one month. Morris water maze was used to examine the learning and memory abilities of the mice. Hematoxylin-eosin staining was employed to observe the pathological and morphological changes of the hippocampus. The immunofluorescence assay was employed to detect the expression of ionized calcium-binding adapter molecule 1(IBA1), glial fibrillary acidic protein(GFAP), chemokine C-X-C-motif ligand 12(CXCL12), chemokine C-X-C-motif receptor 4(CXCR4) in the hippocampus and observe the positional relationship between IBA1, GFAP, and CXCR4. Western blot was employed to determine the protein levels of extracellular regulated kinase(ERK), p-ERK, and tumor necrosis factor receptor 1(TNFR1). Enzyme-linked immunosorbent assay was employed to measure the levels of glutamate and tumor necrosis factor(TNF-α) in the brain tissue and the level of TNF-α in the serum and spleen. Yigong Powder significantly shortened the escape latency, increased the times crossing platforms, and prolonged the cumulative time in quadrants of the aging mice. It alleviated the nerve cell disarrangement, increased intercellular space, and cell degeneration or death in the hippocampus and reduced the pathology score of the damaged nerve. Moreover, Yigong Powder reduced the positive area of IBA1 and GFAP, reduced the levels of TNF-α in the brain tissue, serum, and spleen, and decreased spleen index. Furthermore, Yigong Powder decreased the average fluorescence intensity of CXCL12 and CXCR4, reduced CXCR4-positive astrocytes and microglia, down-regulated the protein levels of p-ERK/ERK and TNFR1, and lowered the level of glutamate in the brain tissue. This study showed that the preventive administration of Yigong Powder can ameliorate the learning and memory decline of the D-galactose-induced aging mice by regulating the immune function of the spleen and the CXCL12/CXCR4 signaling in the brain to reduce glutamate release. However, the mechanism of Yigong San in preventing and treating dementia via regulating spleen and stomach function remains to be studied.

Skin-safe nanophotosensitizers with highly-controlled synthesized polydopamine shell for synergetic chemo-photodynamic therapy.

Although photodynamic therapy (PDT) has been extensively studied as an established modality of cancer treatment, it still suffers from a few clinical limitations, such as skin phototoxicity and tumor hypoxia. To circumvent these hurdles, hollow silica mesoporous nanoparticles (HMSNs) loaded with photosensitizers were employed as the nanoplatform to construct multifunctional nanoparticles (NPs). Specifically, an ultra-uniform polydopamine (PDA) shell was highly controlled grown around HMSNs by photogenerated outwards-diffused 1O2, followed by conjugation of folic acid-poly(ethylene glycol) and chelation of Fe2+ ions. Thanks to the optimal thickness of light-absorbing PDA shell, the multifunctional NPs exhibited not only negligible skin phototoxicity but also efficient 1O2 generation and photothermal (PT)-enhanced •OH generation upon respective photoirradiation. Anti-tumor therapy was then performed on both 4 T1 tumor cells and tumor-bearing mice by the combination of 638 nm PDT and 808 nm PT-enhanced chemodynamic therapy (CDT). As a result, high therapeutic efficacy was achieved compared to single-modality therapy, with a cell inhibitory rate of 86% and tumor growth inhibition of 70.4% respectively. More interestingly, tumor metastasis was effectively inhibited by the synergetic treatment. These results convincingly demonstrate that our multifunctional NPs are very promising skin-safe PDT agents combined with CDT for efficient tumor therapy.

Weakly supervised multitask learning models to identify symptom onset time of unclear-onset intracerebral hemorrhage.

BACKGROUND: Approximately one-third of spontaneous intracerebral hemorrhage patients did not know the onset time and were excluded from studies about time-dependent treatments for hyperacute spontaneous intracerebral hemorrhage. AIMS: To help clinicians explore the benefit of time-dependent treatments for unclear-onset patients, we presented artificial intelligence models to identify onset time using non-contrast computed tomography (NCCT) based on weakly supervised multitask learning (WS-MTL) structure. METHODS: The patients with reliable symptom onset time (strong label) or repeat CT (weak label) were included and split into training set and test set (internal and external). The WS-MTL structure utilized strong and weak labels simultaneously to improve performance. The models included three binary classification models for classifying whether NCCT acquired within 6, 8 or 12 h for different treatments measured by area under curve, and a regression model for determining the exact onset time measured by mean absolute error. The generalizability of models was also explored in comprehensive analysis. RESULTS: A total of 4004 patients with 10,780 NCCT scans were included. The performance of WS-MTL classification model showed high accuracy, and that of regression model was satisfactory in ≤6 h subgroup. In comprehensive analysis, the WS-MTL showed better performance for larger hematomas and thinner scans. And the performance improved effectively as training amounts increasing and could be improved steadily through retraining. CONCLUSIONS: The WS-MTL models showed good performance and generalizability. Considering the large number of unclear-onset spontaneous intracerebral hemorrhage patients, it may be worth to integrate the WS-MTL model into clinical practice to identify the onset time.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study / 中国当代儿科杂志

OBJECTIVES@#To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.@*METHODS@#A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.@*RESULTS@#The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).@*CONCLUSIONS@#It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Multicenter post-marketing clinical evaluation on the clinical performance of the five domestic fast nucleic acid detection reagents for 2019-nCoV / 中华检验医学杂志

Objective:This multicenter clinical evaluation analyzed the clinical performance of five fast nucleic acid detection systems for 2019-nCoV.Methods:Clinical performance of the five fast nucleic acid detection reagents approved in China was evaluated in the present study. Fifty-seven throat swabs samples from COVID-19 patients and fifteen throat swabs samples from healthy people were collected from the First Affiliated Hospital of Zhejiang University school of Medicine, Tongji Hospital of Tongji Medical College of HUST, and National Institute of Viral Disease Control and Prevention of CDC to evaluate the positive coincidence rate, negative coincidence rate, total coincidence rate, the detection time and retest rate as well as the relation between positive intensity and positive coincidence rate of the five fast nucleic acid detection systems in November 2020.Results:The positive coincidence rates of the five kits were 92.59% (50/54), 83.64% (46/55), 98.25% (56/57), 94.44% (51/54) and 98.18% (54/55); and the negative coincidence rates were 93.33% (14/15), 93.33% (14/15), 86.67% (13/15), 100% (14/14) and 93.33% (14/15); and the total coincidence rates were 92.75% (64/69), 85.71% (60/70), 95.83% (69/72), 94.20% (65/69) and 97.14% (68/70), respectively. The positive coincidence rate of the five kits reached 100% for the strong-positive (90/90) and medium-positive samples (84/84), but only 82.18% (83/101) for weak-positive samples (cycle threshold value>33), and the retest rate of two kits were 15.28% (11/72) and 12.50% (9/72), which were both higher than 10%. Total time from sample extraction to amplification was between 32.33-65.33 minutes for these five kits.Conclusion:The five fast nucleic acid detection reagents have good performance and can be used as a supplement to routine nucleic acid detection reagents.

Rapid Formation of Nanoclusters for Detection of Drugs in Urine Using Surface-Enhanced Raman Spectroscopy.

We developed a method based on surface-enhanced Raman spectroscopy (SERS) and a sample pretreatment process for rapid, sensitive, reproducible, multiplexed, and low-cost detection of illegal drugs in urine. The abuse of new psychoactive substances (NPS) has become an increasingly serious problem in many countries. However, immunoassay-based screening kits for NPS are usually not available because of the lack of corresponding antibodies. SERS has a great potential for rapid detection of NPS because it can simultaneously detect multiple kinds of drugs without the use of antibodies. To achieve highly sensitive SERS detection of drugs, sodium bromide was first employed to induce the rapid formation of Ag nanoclusters by aggregating silver nanoparticles (AgNPs) in the extracted sample solution. SERS measurements were performed immediately after the sample pretreatment without incubation. The three-dimensional SERS hot spots were believed to form significantly within the nanoclusters, providing strong SERS enhancement effects. The displacement of citrate molecules on the surfaces of the AgNPs by bromide ions helped increase the adsorption of drug molecules, increasing their areal density. We demonstrated the simultaneous detection of two kinds of NPS, methcathinone and 4-methylmethcathinone, in urine at a concentration as low as 0.01 ppm.

The Patterns of Morphological Change During Intracerebral Hemorrhage Expansion: A Multicenter Retrospective Cohort Study.

Objectives: Hemorrhage expansion (HE) is a common and serious condition in patients with intracerebral hemorrhage (ICH). In contrast to the volume changes, little is known about the morphological changes that occur during HE. We developed a novel method to explore the patterns of morphological change and investigate the clinical significance of this change in ICH patients. Methods: The morphological changes in the hematomas of ICH patients with available paired non-contrast CT data were described in quantitative terms, including the diameters of each hematoma in three dimensions, the longitudinal axis type, the surface regularity (SR) index, the length and direction changes of the diameters, and the distance and direction of movement of the center of the hematoma. The patterns were explored by descriptive analysis and difference analysis in subgroups. We also established a prognostic nomogram model for poor outcomes in ICH patients using both morphological changes and clinical parameters. Results: A total of 1,094 eligible patients from four medical centers met the inclusion criteria. In 266 (24.3%) cases, the hematomas enlarged; the median absolute increase in volume was 14.0 [interquartile range (IQR), 17.9] mL. The initial hematomas tended to have a more irregular shape, reflected by a larger surface regularity index, than the developed hematomas. In subtentorial and deep supratentorial hematomas, the center moved in the direction of gravity. The distance of center movement and the length changes of the diameters were small, with median values of less than 4 mm. The most common longitudinal axis type was anterior-posterior (64.7%), and the axis type did not change between initial and repeat imaging in most patients (95.2%). A prognostic nomogram model including lateral expansion, a parameter of morphological change, showed good performance in predicting poor clinical outcomes in ICH patients. Conclusions: The present study provides a morphological perspective on HE using a novel automatic approach. We identified certain patterns of morphological change in HE, and we believe that some morphological change parameters could help physicians predict the prognosis of ICH patients.

Prevention and control of HIV/AIDS in China: lessons from the past three decades / 中华医学杂志(英文版)

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Selection of enteral nutrition regimens for children with abdominal Henoch-Schönlein purpura / 中国当代儿科杂志

OBJECTIVE@#To explore the reasonable and effective enteral nutrition regimen for children with abdominal Henoch-Schönlein purpura (HSP).@*METHODS@#A retrospective analysis was performed on the medical data of children with abdominal HSP who were hospitalized from August 2013 to August 2018. According to the starting time of enteral nutrition after abdominal pain relief, the children were divided into three groups: < 24 hours (@*RESULTS@#The retrospective analysis showed that the children who were given extensively hydrolyzed lactoprotein formula for enteral nutrition at 24-48 hours after abdominal pain relief had a lower recurrence rate of clinical symptoms and the highest degree of satisfaction among their family members (@*CONCLUSIONS@#It is reasonable and effective to start the feeding with extensively hydrolyzed lactoprotein formula at 24-48 hours after abdominal pain relief in children with abdominal HSP.

Effect of drying processing methods on different specifications of Sophorae Flos based on comprehensive statistical analysis / 中国中药杂志

To investigate the effects of six common drying methods on the quality of different specifications of Sophorae Flos, in order to select their suitable drying methods. According to appearance and morphology, Sophorae Flos was divided into the following three specifications: flower bud type(HL), half-open type(BK) and blooming type(SK). All specifications of samples were treated with shade-drying method(25 ℃, natural temperature), sun-drying method, hot-air-drying method(60, 105 ℃), and drying method(60 ℃) after steaming. The contents of total flavonoids, rutin, narcissus, quercetin, isorhamnetin, and Fe~(3+) reducing ability, DPPH free radical scavenging ability, ABTS free radical scavenging ability and fluorescence recovery after photobleaching(FRAP) were detected by UV, HPLC and colorimetry, respectively. Principal component analysis(PCA), cluster analysis(CA) and correlation analysis were used to comprehensively evaluate the quality of samples. According to the results, there were significant differences in the effect of drying methods on different specifications of samples. The drying method(60 ℃) after steaming was suitable for HL and BK, while the hot-air-drying method(60 ℃) was suitable for SK. When the fresh medicinal materials could not be treated in time, they should be spread out in a cool and ventilated place. Under high and low temperature conditions, the quality of three specifications of Sophorae Flos would be reduced. The hot-air-drying method(105 ℃) and shade-drying method(25 ℃) were not suitable for the treatment of fresh flowers and flower buds of Sophora japonicus. There were obviously differences of chemical compositions and antioxidant activities among the three specifications of samples. Therefore, the specifications of medicinal materials should be controlled to ensure the uniform quality. The study provided the abundant data reference for the selection of appropriate drying methods for the three specifications of Sophorae Flos, and useful exploration for the classification and processing of medicinal materials of flowers.

Luminescent ruthenium(II)-containing metallopolymers with different ligands: synthesis and application as oxygen nanosensor for hypoxia imaging.

A series of Ru(II)-containing metallopolymers with different polypyridyl complexes, namely [Ru(N^N)2(L)](PF6)2 (L = bipyridine-branched polymer; N^N = bpy: 2,2'-bipyridine (Ru 1); phen: 1,10-phenanthroline (Ru 2); dpp: 4,7-diphenyl-1,10-phenanthroline (Ru 3)), were synthesized with the motive that adjusting π-conjugation length of ligands might produce competent luminescent oxygen probes. The three hydrophobic metallopolymers were studied with 1H NMR, UV-Vis absorption, and emission spectroscopy, and then were utilized to prepare biocompatible nanoparticles (NPs) via a nanoprecipitation method. Luminescent properties of the NPs were investigated against dissolved oxygen by steady-state and time-resolved spectroscopy respectively. Luminescence quenching of the three NPs all followed a linear behavior in the range of 0-43 ppm (oxygen concentration), but Ru 3-NPs exhibited the highest oxygen sensitivity (82%) and longest emission wavelength (λex = 460 nm; λem = 617 nm). In addition, external interferons from cellular environments (e.g., pH, temperature, and proteins) had been studied on Ru 3-NPs. Finally, dissolved oxygen in monolayer cells under normoxic/hypoxic conditions was clearly differentiated by using Ru 3-NPs as the luminescent sensor, and, more importantly, hypoxia within multicellular tumor spheroids was vividly imaged. These results suggest that such Ru(II)-containing metallopolymers are strong candidates for luminescent nanosensors towards hypoxia. Graphical abstract.

Facile synthesis of polypyrrole-rhodamine B nanoparticles for self-monitored photothermal therapy of cancer cells.

Photothermal therapy following microscopic temperature detection can avoid overheating effects or insufficient heating, and thus improve therapeutic efficacy. In this study, biocompatible dual-functional nanoparticles (NPs) are constructed from polypyrrole (PPy) and rhodamine B (RB) by a one-step modified polymerization method. The polypyrrole serves as a photothemal agent, and rhodamine B acts as a temperature-sensing probe. The polypyrrole-rhodamine B (PPy-RB) NPs possess a high photothermal effect on irradiation by 808 nm laser, and a competent temperature sensitivity for the real-time temperature monitoring based on the emission intensity response of rhodamine B. After acting on HepG2 cells, the PPy-RB NPs can effectively induce cancer cell death, and the microscopic temperature is monitored by fluorescence feedback from rhodamine B during PTT by laser confocal microscopy. Hence, the proposed approach can supply a facile and promising way for the fabrication of effective theranostic nanoplatforms assisted by self-monitoring of cancer therapeutic processes.

Facile synthesis of multifunctional nanoparticles encoded with quantum dots and magnetic nanoparticles: cell tagging and MRI.

In this study, fluorescence-encoded magnetic biocompatible nanoparticles (NPs) were constructed from CdSe@ZnS quantum dots (QDs) and Fe3O4 nanoparticles with a one-step reprecipitation-encapsulation method. The resultant hybrid NPs exhibit small size (∼130 nm in diameter), highly bright QDs, two-color emissions (green and red) under single-wavelength excitation, easy separation with a magnet and efficient cellular internalization. Energy transfer between the incorporated QDs was studied to better tailor the encoded fluorescence, and 11 barcodes were obtained by adjusting the ratio of green and red QDs. We used four sets of the barcodes to tag specific cancer cells (HepG2) as a proof-of-concept, and distinguished each set according to respective overlayed fluorescence images using laser confocal microscopy. Moreover, the incorporated Fe3O4 NPs endowed as-constructed optical barcode superparamagnetic property by T 2-enhanced magnetic resonance effect with an r 2 value of 145.25 s-1 mM-1 at 3 T. These results suggest that the multifunctional NPs are very promising for discriminating different cells and dual-modality imaging.

Construction of laboratory medicine suitable for large-scale public health events / 中华检验医学杂志

The medical laboratories have played the important role in fighting against the pandemic of COVID-19. It′s critical to improve response strategy and better prepare to create robust and sustainable medical laboratories for future outbreaks of public health events. The general framework to guide the construction of the qualified medical laboratories is discussed.

Optimization of water extracting and refining procession of Sijunzi Decoction Granules by orthogonal design and pharmacodynamics test / 中草药

Objective: To optimize the water extracting and refining procession of Sijunzi Decoction Granules (SDG). Methods: The orthogonal test method was used to study the four factors including the soak time, amount of water added, extraction time and frequency by taking the dry extract yield of the medicinal materials and contents of ginsenoside Rg1, Re, Rb1, glycyrrhizic acid, and liquiritin as indicators to optimize the water extracting process of SDG. To optimize the alcohol precipitation process of SDG, the factors including the concentration of the medicinal materials, alcohol content, and time of alcohol precipitation were investigated. The extracts before and after alcohol precipitation were compared by intervening spleen deficiency syndrome pharmacodynamics experiment. Results: The best water extracting procession of SDG was soaked for 60 min with 10 times of water, decocted three times, 30 min for each time. The optimal water extraction by alcohol sedimentation process was to concentrate the filtrate of water extraction to 1 mL, which was equivalent to 0.5 g of the original medicinal materials, with 80% alcohol content and 12 h alcohol precipitation time. Compared with the model group, the activity of salivary amylase and the conent of serum gastrin in the water extracting group and water extracting by alcohol sedimentation group of SDG were significantly increased and could improve the absorption function of xylose in small intestine of rats with spleen deficiency syndrome (P 0.05). Conclusion: The alcohol precipitation process is not suitable for refining of SDG. So the water extracting process is finally selected as the best extraction process of SDG.

Disparity of human immunodeficiency virus incidence and drug resistance in college student, non-student youth and older men who have sex with men: a cross-sectional study from seven major cities of China / 中华医学杂志(英文版)

BACKGROUND@#Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM.@*METHODS@#We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, <25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance.@*RESULTS@#Overall, 4,496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1,094 NSYM, and 2,837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100PY, 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100PY, and TDR prevalence were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age< 21-year-old, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (AOR: 2.5; 95% CI: 1.0-5.8).@*CONCLUSIONS@#College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.

Polylysine modified conjugated polymer nanoparticles loaded with the singlet oxygen probe 1,3-diphenylisobenzofuran and the photosensitizer indocyanine green for use in fluorometric sensing and in photodynamic therapy.

Conjugated polymer hybrid nanoparticles (NPs) loaded with both indocyanine green (ICG) and 1,3-diphenylisobenzofuran (DPBF) are described. The NPs are dually functional in that ICG acts as the photosensitizer, and DPBF as a probe for singlet oxygen (1O2 probe). The nanoparticle core consists of the energy donating host poly(9,9-dioctylfluorenyl-2,7-diyl)-co-(2,5-p-xylene) (PFP). The polymer is doped with the energy acceptor DPBF. Ratiometric fluorometric detection of singlet oxygen is accomplished by measurement of fluorescence at wavelengths of 415 and 458 nm. In addition, the shell of the positively charged polymeric nanoparticles was modified, via electrostatic interaction, with negatively charged PDT drugs ICG. The integrated nanoparticles of type ICG-DPBF-PFP display effective photodynamic performance under 808-nm laser irradiation. The 1O2 sensing behaviors of samples are evaluated based on the ratiometric fluorescent responses produced by DPBF and PFP. 1O2 can be fluorimetically sensed with a detection limit of 28 µM. The multifunctional nanoprobes exhibit effortless cellular uptake, superior photodynamic activity and a rapid ratiometric response to 1O2. Graphical abstractSchematic of a dual-functional nanoplatform for photodynamic therapy (PDT) and singlet oxygen (1O2) feedback. It offers a new strategy for self-monitoring photodynamic ablation. FRET: fluorescence resonance energy transfer. Indocyanine green is attached in the shell of nanoparticles, and 1,3-diphenylisobenzofuran is doped into the energy donating host conjugated polymer.

Ratiometric Luminescent Nanoprobes Based on Ruthenium and Terbium-Containing Metallopolymers for Intracellular Oxygen Sensing.

A collection of luminescent metal complexes have been widely used as oxygen probes in the biomedical field. However, single intensity-based detection approach usually suffered from errors caused by the signal heterogeneity or fluctuation of the optoelectronic system. In this work, respective ruthenium (II) and terbium (III) complexes were chosen to coordinate a bipyridine-branched copolymer, so that to produce oxygen-sensitive metallopolymer (Ru-Poly) and oxygen-insensitive metallopolymer (Tb-Poly). Based on the hydrophobic Ru-Poly and Tb-Poly, a ratiometric luminescent oxygen nanoprobe was facilely prepared by a nanoprecipitation method. The nanoprobes have a typical size of ~100 nm in aqueous solution, exhibiting a green-red dual-wavelength emission under the excitation of 300 nm and 460 nm, respectively. The red emission is strongly quenched by dissolved oxygen while the green one is rather stable, and the ratiometric luminescence was well fitted by a linear Stern-Volmer equation. Using the ratiometric biocompatible nanoprobes, the distribution of intracellular oxygen within three-dimensional multi-cellular tumor spheroids was successfully imaged.

Facile synthesis of fluorinated nanophotosensitizers with self-supplied oxygen for efficient photodynamic therapy.

Tumor hypoxia severely reduces the efficiency of photodynamic therapy (PDT) through the insufficient supply of oxygen. In this work, we reported on a design of fluorinated nanophotosensitizers (NPSs) prepared by a facile reprecipitation-encapsulation method, with the aim of addressing the issue of hypoxia. The fluorinated NPSs consisted of a hybrid particle core of perfluorosiloxane-polystyrene, doped with a fluorinated photosensitizer, and a biocompatible poly-l-lysine shell. Compared with non-fluorinated counterpart NPSs that are similarly prepared except for the replacement of perfluorosiloxane with alkoxysilane, the fluorinated NPSs saturated with O2 exhibit approximately 3.5 fold higher singlet oxygen production yield and higher in vitro PDT efficiency due to the O2-carrying capability of intra-particle 'F-C' bonds.

Highly Stable and Luminescent Oxygen Nanosensor Based on Ruthenium-Containing Metallopolymer for Real-Time Imaging of Intracellular Oxygenation.

Metal complex-based luminescent oxygen nanosensors have been intensively studied for biomedical applications. In terms of monitoring dynamics of intracellular oxygen, however, high-quality nanosensors are still badly needed, because of stringent requirements on stability, biocompatibility and luminescence intensity, aside from oxygen sensitivity. In this paper, we reported a type of highly luminescent and stable oxygen nanosensors prepared from metallopolymer. First, a novel ruthenium(II)-containing metallopolymer was synthesized by chelating the oxygen probe [Ru(bpy)3]2+ with a bipyridine-branched hydrophobic copolymer, which was then doped into polymeric nanoparticles (NPs) by a reprecipitation method, followed by further conjugation to selectively target mitochondria (Mito-NPs). The resultant Mtio-NPs possessed a small hydrodynamic size of ∼85 nm, good biocompatibility and high stability resulting from PEGylation and stable nature of Ru-complex. Because the complexed [Ru(bpy)3]2+ homogeneously resided on particle surface, Mito-NPs exhibited strong luminescence at 608 nm that was free of aggregation-caused-quenching, the utmost oxygen sensitivity of free [Ru(bpy)3]2+ probe ( Q = 75%), and linear Stern-Volmer oxygen luminescence quenching plots. Taking advantage of the mitochondria-specific nanosensors, intracellular oxygenation and deoxygenation processes were real-time monitored for 10 min by confocal luminescence imaging, visualized by the gradual weakening (by more than 90%) and enhancing (by 50%) of the red emission, respectively.