The Pharmacological Mechanism of the Effect of Plant Extract Compound Drugs on Cancer Pain Based on Network Pharmacology.

Objective: We systematically analyzed the mechanism of plant-derived drugs alleviating cancer pain in our hospital through network pharmacology, so as to provide the possibility of further application of traditional Chinese medicine in the treatment of cancer pain. Methods: We used TCMSP, ETCM, and TCMID databases to mine the active ingredients of plant-derived drugs. We combined OMIM, GeneCards, and DrugBank databases to mine and match the common targets of plant-derived drugs for cancer pain. We used the STRING platform and Cytoscape software to analyze and screen out the core targets. We used GO and KEGG methods to analyze the biological processes, molecular functions, cellular composition, and signaling pathways involved in the reduction of cancer pain by plant-derived drugs. Results: We found 153 active ingredients from botanical drugs by TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP), ETCM (The Encyclopedia of Traditional Chinese Medicine), and TCMID (Traditional Chinese Medicine Integrated Database) databases, covering 341 protein targets in human body. Combined with OMIM (Online Mendelian Inheritance in Man), GeneCards, and DrugBank databases, we excavated and matched 141 targets of plant-derived drugs and cancerous pain diseases. Through the analysis of the STRING platform and Cytoscape software, 19 core targets including TNF, MAPK1, JUN, and IL-6 were screened out. Go and KEGG enrichment showed that plant-derived drugs alleviated cancer pain processes involving 193 biological processes, 47 molecular functions, 22 cell components, and 118 signaling pathways. By screening genes involved in KEGG signaling pathway, it was found that plant-derived drugs were mainly associated with PI3K-Akt signaling pathway, tumor necrosis factor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway in alleviating cancer pain. Conclusion: These results indicate that botanical drugs can positively affect the expression of inflammatory factors and apoptotic factors in the process of treatment and relief of cancer pain, which is expected to have a potential therapeutic effect on the relief of cancer pain.

Effects of Bacillus subtilis and Bacillus licheniformis on growth performance, immunity, short chain fatty acid production, antioxidant capacity, and cecal microflora in broilers.

This study investigated the effects of dietary supplementation with Bacillus subtilis (B. subtilis) or Bacillus licheniformis (B. licheniformis) on growth performance, immunity, antioxidant capacity, short chain fatty acid (SCFA) production, and the cecal microflora in broiler chickens. In total, 360 male, 1-day-old Cobb 500 birds were randomly divided into 3 groups: the control group was fed a basal diet; the B. subtilis group was fed a basal diet supplemented with 1.5 × 109 CFU/kg B. subtilis; the B. licheniformis group was fed a basal diet supplemented with 1.5 × 109 CFU/kg B. licheniformis. Results showed that chickens supplemented with either B. subtilis or B. licheniformis had comparatively higher (P < 0.05) body weight and average daily gain, whereas no difference (P > 0.05) was observed in feed efficiency. Concentrations of serum IgA, IgY, and IgM, as well as anti-inflammatory IL-10 were significantly increased (P < 0.05), and proinflammatory IL-1ß and IL-6 were significantly decreased (P < 0.05) by B. subtilis or B. licheniformis supplementation. Moreover, chickens fed with diets supplemented by either B. subtilis or B. licheniformis had greater antioxidant capacity, indicated by the notable increases (P < 0.05) in glutathione peroxidase, superoxide dismutase, and catalase, along with decrease (P < 0.05) in malondialdehyde. Compared to the control group, levels of SCFA, excluding acetic and propionic acid, in cecal content had improved (P < 0.05) by adding B. licheniformis, and significant increase (P < 0.05) in acetic and butyric acid was observed with B. subtilis supplementation. Microbial analysis showed that both B. subtilis or B. licheniformis supplementation could increase butyrate-producing bacteria such as Alistipes and Butyricicoccus, and decrease pathogenic bacteria such as the Synergistetes and Gammaproteobacteria. In summary, dietary supplemented with B. subtilis or B. licheniformis improved growth performance, immune status, and antioxidant capacity, increased SCFA production, and modulated cecal microbiota in chickens. Moreover, B. licheniformis was more effective than B. subtilis with the same supplemental amount.

New Insights Into the Biosynthesis of Typical Bioactive Components in the Traditional Chinese Medicinal Fungus Cordyceps militaris.

Cordyceps militaris, a traditional medicinal ingredient with a long history of application in China, is regarded as a high-value fungus due to its production of various bioactive ingredients with a wide range of pharmacological effects in clinical treatment. Several typical bioactive ingredients, such as cordycepin, D-mannitol, cordyceps polysaccharides, and N6-(2-hydroxyethyl)-adenosine (HEA), have received increasing attention due to their antitumor, antioxidant, antidiabetic, radioprotective, antiviral and immunomodulatory activities. Here, we systematically sorted out the latest research progress on the chemical characteristics, biosynthetic gene clusters and pathways of these four typical bioactive ingredients. This summary will lay a foundation for obtaining low-cost and high-quality bioactive ingredients in large amounts using microbial cell factories in the future.

Insight on the changes of cassava and potato starch granules during gelatinization.

Gelatinization is an important property of starch for biomedical applications. However, studies on the changes in starch granules in terms of morphology, swelling, amylose leaching and so on during gelatinization, which are key to uncovering the starch gelatinization process, have rarely been reported. Herein, changes of cassava and potato starch granules during gelatinization were investigated. It was found that there is a substantial difference in the granule changes during gelatinization between cassava and potato starch. Cassava starch granules remain intact with slight swelling, with approximately 8.5% amylose leaching in water for 30 min at 60 °C. In sharp contrast, potato starch granules swell very well and rapidly, losing much integrity with 51.05% amylose leaching. The gelatinization time and temperature have much greater effects on the changes of potato starch granules than cassava starch granules.

Effects of Phytoremediation Treatment on Bacterial Community Structure and Diversity in Different Petroleum-Contaminated Soils.

Increased exploitation and use of petroleum resources is leading to increased risk of petroleum contamination of soil and groundwater. Although phytoremediation is a widely-used and cost-effective method for rehabilitating soils polluted by petroleum, bacterial community structure and diversity in soils undergoing phytoremediation is poorly understood. We investigate bacterial community response to phytoremediation in two distinct petroleum-contaminated soils (add prepared petroleum-contaminated soils) from northwest China, Weihe Terrace soil and silty loam from loess tableland. High-throughput sequencing technology was used to compare the bacterial communities in 24 different samples, yielding 18,670 operational taxonomic units (OTUs). The dominant bacterial groups, Proteobacteria (31.92%), Actinobacteria (16.67%), Acidobacteria (13.29%) and Bacteroidetes (6.58%), increased with increasing petroleum concentration from 3000 mg/kg⁻10,000 mg/kg, while Crenarchaeota (13.58%) and Chloroflexi (4.7%) decreased. At the order level, RB41, Actinomycetales, Cytophagales, envOPS12, Rhodospirillales, MND1 and Xanthomonadales, except Nitrososphaerales, were dominant in Weihe Terrace soil. Bacterial community structure and diversity in the two soils were significantly different at similar petroleum concentrations. In addition, the dominant genera were affected by available nitrogen, which is strongly associated with the plants used for remediation. Overall, the bacterial community structure and diversity were markedly different in the two soils, depending on the species of plants used and the petroleum concentration.

3D printing and coating to fabricate a hollow bullet-shaped implant with porous surface for controlled cytoxan release.

Intratumoral implants have aroused great interests for local chemotherapy of cancer, however, how to efficiently control drug release from implants is still a great challenge. Herein, we designed and prepared a new hollow bullet-shaped implant with porous surface by 3D printing, loaded chemotherapeutic agent cytoxan (CTX) with tetradecyl alcohol or lecithin as matrix and coated it with poly (lactic acid) to obtain a CTX implant, which has a highly tuned drug release property with a drug release time from 4 h to more than 1 month. The drug release from the implant can be easily controlled by changing pore sizes, kinds of matrices, and coating thickness.

Glutathione detonated and pH responsive nano-clusters of Au nanorods with a high dose of DOX for treatment of multidrug resistant cancer.

Effects of nanosized drug delivery systems on cancer are often compromised due to their low drug loadings, premature drug release and multi-drug resistance (MDR). Herein, we reported a glutathione detonated and pH responsive nano-cluster of Au nanorods (AuNRs) with chemotherapeutic doxorubicin (DOX) and pre-chemosensitizer polycurcumin to treat MCF-7/ADR cells. The nano-cluster was prepared by self-assembling of AuNRs conjugated with DOX and amphiphilic poly(curcumin-co-dithiodipropionic acid)-b-biotinylated poly(ethylene glycol) via an emulsion/solvent evaporation technique, termed AuNR Cluster. The AuNR Cluster had a high drug loading (31.5% DOX), presenting much better aqueous solubility and stability at physiological pH than their individual AuNRs. The AuNR Cluster could be detonated to be their individual AuNRs at an intracellular concentration level of glutathione (GSH) (5 mM) and triggered to release DOX at an acidic pH (pH 6.8 or 5.0), which effectively facilitated cellular uptake of DOX (607 vs 356 a.u. for AuNRs at 12 h) and inhibited DOX efflux (471.33 vs 39.17 a.u. for free DOX at 24 h). The IC50 value of DOX against MCF-7/ADR cells for AuNR Cluster was 4.15 µg/mL, much lower than that for free DOX (90.97 µg/mL). The AuNR Cluster took much more photothermal effects than their corresponding AuNRs and presented enhanced anti-tumor effect (IC50: 2.61 µg/mL) under 808 nm laser irradiation. STATEMENT OF SIGNIFICANCE: Nano-sized drug delivery systems for anti-MDR cancer is still a challenging task. Herein, AuNR Cluster was self-assembled by individual AuNRs via emulsion/solvent evaporation technique, having a structure consisting of hydrophobic DOX/PCDA-AuNR core and hydrophilic biotin-PEG chain shell. AuNR Cluster is detonated to disintegrate and yield its individual AuNRs at an intracellular concentration level of glutathione (5 mM) and triggered to release DOX at an acidic pH (6.8 or 5.0). In comparison with its individual AuNRs, AuNR Cluster has better water solubility and stability, greater photothermal effects under NIR irradiation, bigger cytotoxicity against MCF-7/ADR cells. AuNR Cluster is expected to be a potential nanomedicine for treatment of MDR cancer.

Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy.

Rationale: Treatment for Parkinson's disease (PD) is challenged by the presence of the blood-brain barrier (BBB) that significantly limits the effective drug concentration in a patient's brain for therapeutic response throughout various stages of PD. Curcumin holds the potential for α-synuclein clearance to treat PD; however, its applications are still limited due to its low bioavailability and poor permeability through the BBB in a free form. Methods: Herein, this paper fabricated curcumin-loaded polysorbate 80-modified cerasome (CPC) nanoparticles (NPs) with a mean diameter of ~110 nm for enhancing the localized curcumin delivery into the targeted brain nuclei via effective BBB opening in combination with ultrasound-targeted microbubble destruction (UTMD). Results: The liposomal nanohybrid cerasome exhibited superior stability towards PS 80 surfactant solubilization and longer circulation lifetime (t1/2 = 6.22 h), much longer than free curcumin (t1/2 = 0.76 h). The permeation was found to be 1.7-fold higher than that of CPC treatment only at 6 h after the systemic administration of CPC NPs. Notably, motor behaviors, dopamine (DA) level and tyrosine hydroxylase (TH) expression all returned to normal, thanks to α-synuclein (AS) removal mediated by efficient curcumin delivery to the striatum. Most importantly, the animal experiment demonstrated that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice had notably improved behavior disorder and dopamine depletion during two-week post-observation after treatment with CPC NPs (15 mg curcumin/kg) coupled with UTMD. Conclusion: This novel CPC-UTMD formulation approach could be an effective, safe and amenable choice with higher therapeutic relevance and fewer unwanted complications than conventional chemotherapeutics delivery systems for PD treatment in the near future.

Near-infrared triggered co-delivery of doxorubicin and quercetin by using gold nanocages with tetradecanol to maximize anti-tumor effects on MCF-7/ADR cells.

Previously, combination chemotherapy of doxorubicin (DOX) and quercetin (QUR) was developed to improve antitumor effects and reverse multidrug resistance and several biocompatible nanocarriers, such as liposomes and micelles, were validated for their targeted delivery. In this study, we report a near-infrared (NIR)-responsive drug delivery system based on DOX and QUR co-loaded gold nanocages (AuNCs) with biotin modification. The system was simply fabricated by filling the hollow interiors of AuNCs with tetradecanol (TD), a phase-change material with a melting point of 39°C, to control the drug release. The main cause of multidrug resistance (MDR) of DOX is the overexpression of P-glycoprotein (P-gp), which can be inhibited by QUR. Thus the combination chemotherapy of DOX and QUR may provide a promising strategy for MDR. The in vitro cytotoxicity of DOX and QUR at several fixed mass ratios was carried out and showed that the combination index (CI) was the smallest at the ratio of 1:0.2, indicating that the best synergistic effect was achieved. The resultant nanocomplex (abbreviated as BPQD-AuNCs) exhibited fast release (80% released in 20min) and strong cytotoxicity against MCF-7/ADR cells (IC50, 1.5µg/mL) under NIR irradiation. Additionally, BPQD-AuNCs were found to generate a large amount of reactive oxygen species (ROS), to inhibit P-gp expression and ATP activity. Taken together, the results show that BPQD-AuNC is a prospective nano-delivery system for overcoming multidrug-resistant cancer.

A new NIR-triggered doxorubicin and photosensitizer indocyanine green co-delivery system for enhanced multidrug resistant cancer treatment through simultaneous chemo/photothermal/photodynamic therapy.

It is a great challenge to combat multidrug resistant (MDR) cancer effectively. To address this issue, we developed a new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39°C, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells. This nano-sized system was constructed by filling the interior of AuNCs with DOX, ICG and 1-tetradecanol, and modifying the surface with biotinylated poly (ethylene glycol) via Au-S bonds, termed as DOX/ICG@biotin-PEG-AuNC-PCM. The DOX and ICG co-release from DOX/ICG@biotin-PEG-AuNC-PCM was much faster in PBS at 40°C or under 808nm NIR irradiation at 2.5W/cm2 than at 37°C (e.g. 67.27% or 80.31% vs. 5.57% of DOX, 76.08% vs. 3.83% of ICG for 20min). The flow cytometry and confocal laser scanning microscopy (CLSM) results showed, the AuNCs were taken up by MCF-7/ADR cells via endocytosis, thus enhancing DOX uptake; the biotin on AuNCs facilitated this endocytosis; NIR irradiation caused the heating of the AuNCs, triggering the DOX and ICG co-release and enhancing the distribution of DOX in nuclei, the released ICG generated ROS to take photodynamic therapy. Due to the above unique properties, DOX/ICG@biotin-PEG-AuNC-PCM exerted excellent anti-tumor effects under NIR irradiation, its IC50 against MCF-7/ADR cells was very low, only 0.48µg/mL, much smaller than that of free DOX (74.51µg/mL). STATEMENT OF SIGNIFICANCE: A new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39°C, was prepared, termed as DOX/ICG@biotin-PEG-AuNC-PCM, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells. DOX/ICG@biotin-PEG-AuNC-PCM exerted excellent anti-tumor effects under NIR irradiation, its IC50 against MCF-7/ADR cells was very low, only 0.48µg/mL, much smaller than that of free DOX (74.51µg/mL).

A multifunctional poly(curcumin) nanomedicine for dual-modal targeted delivery, intracellular responsive release, dual-drug treatment and imaging of multidrug resistant cancer cells.

A multifunctional anti-cancer nanomedicine based on a biotin-poly(ethylene glycol)-poly(curcumin-dithio dipropionic acid) (Biotin-PEG-PCDA) polymeric nanocarrier loaded with paclitaxel (PTX), magnetic nanoparticles (MNPs) and quantum dots (QDs) is developed. It combines advantageous properties of efficient targeted delivery and uptake (via biotin and MNP), intracellular responsive release (via cleavable PCDA polymer), fluorescence imaging (via QD) and combined PTX-curcumin dual-drug treatment, allowing for overcoming drug resistance mechanisms of model multidrug resistant breast cancer cells (MCF-7/ADR). The PTX/MNPs/QDs@Biotin-PEG-PCDA nanoparticles are highly stable under physiological conditions, but are quickly disassembled to release their drug load in the presence of 10 mM glutathione (GSH). The nanoparticles show high uptake by tumour cells from a combined effect of magnet targeting and biotin receptor-mediated internalization. Moreover, curcumin, an intracellularly cleaved product of PCDA, can effectively down regulate the expression of drug efflux transporters such as P-glycoprotein (P-gp) to increase PTX accumulation within target cancer cells, thereby enhancing PTX induced cytotoxicity and therapeutic efficacy against MCF-7/ADR cells. Taken together, this novel tumour-targeting and traceable multifunctional nanomedicine is highly effective against model MDR cancer at the cellular level.

Nitinol stents loaded with a high dose of antitumor 5-fluorouracil or paclitaxel: esophageal tissue responses in a porcine model.

BACKGROUND: A poor prognosis associated with esophageal cancer leads to surgical resection not suitable for most patients. Nitinol stents loaded with 50% 5-fluorouracil (5-FU) or paclitaxel (PTX), functioning both as a stent and local chemotherapy, could provide a new therapy modality for these patients. OBJECTIVE: To investigate esophageal tissue responses to nitinol stents loaded with 50% 5-FU or PTX implanted in the esophagus of healthy pigs. DESIGN: Twenty-three healthy Bama mini-pigs were randomly divided into 4 groups for stent implantation: group A (PTX stent, n = 13), group B (5-FU stent, n = 8), group C (blank film-covered stent, n = 1), and group D (bare stent, n = 1). Tissue responses were observed by endoscopy or pathologic analyses, and 5-FU or PTX concentrations were measured in the esophagus at the stent implantation site at different time points. SETTING: Animal laboratory. INTERVENTIONS: Endoscopic placement of esophagus stent. MAIN OUTCOME MEASUREMENTS: Endoscopic examination, histology, and drug concentration analysis. RESULTS: In general, the esophageal tissue responses varied according to different parts of 5-FU or PTX stent (middle part [drug-containing part] and bare ends [drug-free part]). Severe tissue responses at the bare ends of the stent included inflammation, ulceration, and granulation. However, the tissue responses were greatly reduced in the middle part of the stent. The drug concentrations in the esophagus that had contact with the 5-FU stent or PTX stent were very high, especially for the first period after implantation, which did not cause obvious tissue damage. LIMITATION: Some subjects had incomplete follow-up because of unexpected deaths and stent migration. CONCLUSION: The nitinol stents loaded with 50% 5-FU or PTX did not cause severe esophageal tissue responses, although there was a large concentration of the drug in these tissues.

The role of viscosity estimation for oil-in-gelatin phantom in shear wave based ultrasound elastography.

Shear wave based ultrasound elastography utilizes mechanical excitation or acoustic radiation force to induce shear waves in deep tissue. The tissue response is monitored to obtain elasticity information about the tissue. During the past two decades, tissue elasticity has been extensively studied and has been used in clinical disease diagnosis. However, biological soft tissues are viscoelastic in nature. Therefore, they should be simultaneously characterized in terms of elasticity and viscosity. In this study, two shear wave-based elasticity imaging methods, shear wave dispersion ultrasound vibrometry (SDUV) and acoustic radiation force impulsive (ARFI) imaging, were compared. The discrepancy between the measurements obtained by the two methods was analyzed, and the role of viscosity was investigated. To this end, four types of gelatin phantoms containing 0%, 20%, 30% and 40% castor oil were fabricated to mimic different viscosities of soft tissue. For the SDUV method, the shear elasticity µ1 was 3.90 ± 0.27 kPa, 4.49 ± 0.16 kPa, 2.41 ± 0.33 kPa and 1.31 ± 0.09 kPa; and the shear viscosity µ2 was 1.82 ± 0.31 Pa•s, 2.41 ± 0.35 Pa•s, 2.65 ± 0.13 Pa•s and 2.89 ± 0.14 Pa•s for 0%, 20%, 30% and 40% oil, respectively in both cases. For the ARFI measurements, the shear elasticity µ was 7.30 ± 0.20 kPa, 8.20 ± 0.31 kPa, 7.42 ± 0.21 kPa and 5.90 ± 0.36 kPa for 0%, 20%, 30% and 40% oil, respectively. The SDUV results demonstrated that the elasticity first increased from 0% to 20% oil and then decreased for the 30% and 40% oil. The viscosity decreased consistently as the concentration of castor oil increased from 0% to 40%. The elasticity measured by ARFI showed the same trend as that of the SDUV but exceeded the results measured by SDUV. To clearly validate the impact of viscosity on the elasticity estimation, an independent measurement of the elasticity and viscosity by dynamic mechanical analysis (DMA) was conducted on these four types of gelatin phantoms and then compared with SDUV and ARFI results. The shear elasticities obtained by DMA (3.44 ± 0.31 kPa, 4.29 ± 0.13 kPa, 2.05 ± 0.29 kPa and 1.06 ± 0.18 kPa for 0%, 20%, 30% and 40% oil, respectively) were lower than those by SDUV, whereas the shear viscosities obtained by DMA (2.52 ± 0.32 Pa·s, 3.18 ± 0.12 Pa·s, 3.98 ± 0.19 Pa·s and 4.90 ± 0.20 Pa·s for 0%, 20%, 30% and 40% oil, respectively) were greater than those obtained by SDUV. However, the DMA results showed that the trend in the elasticity and viscosity data was the same as that obtained from the SDUV and ARFI. The SDUV results demonstrated that adding castor oil changed the viscoelastic properties of the phantoms and resulted in increased dispersion of the shear waves. Viscosity can provide important and independent information about the inner state of the phantoms, in addition to the elasticity. Because the ARFI method ignores the dispersion of the shear waves, namely viscosity, it may bias the estimation of the true elasticity. This study sheds further light on the significance of the viscosity measurements in shear wave based elasticity imaging methods.

Enhancing curcumin anticancer efficacy through di-block copolymer micelle encapsulation.

We report herein the development of a novel aqueous formulation and improved antitumor activity for curcumin by encapsulating it into a biocompatible and biodegradable poly(L-lactic acid) based poly(anhydride-ester)-b-poly(ethylene glycol) (PAE-b-PEG) micelle. The resulting curcumin loaded micelles were completely water-dispersible, overcoming the problem of poor water solubility that limited its efficacy and bioavailability. In vitro cellular studies revealed that the curcumin-loaded micelles were taken up mainly via endocytosis route and exhibited higher cytotoxicities toward model cancer cell lines (HeLa and EMT6) than free curcumin. An in vivo biodistribution study revealed that the curcumin-loaded micelles displayed significantly enhanced accumulation inside the tumor of EMT6 breast tumor-bearing mice. More impressively, the curcumin-loaded micelles showed stronger antitumor activity, higher anti-angiogenesis effects and induced apoptosis on the EMT6 breast tumor model bearing mice than free curcumin. Furthermore, the curcumin-loaded micelles showed no significant toxicity towards hemotological system, major organs or tissues in mice. Combined with a high antitumor activity and low toxic side-effects, the curcumin-loaded micelles developed here thus appear to be a highly attractive nanomedicine for effective, targeted cancer therapy.

Electrochemiluminescence energy transfer-promoted ultrasensitive immunoassay using near-infrared-emitting CdSeTe/CdS/ZnS quantum dots and gold nanorods.

The marriage of energy transfer with electrochemiluminescence has produced a new technology named electrochemiluminescence energy transfer (ECL-ET), which can realize effective and sensitive detection of biomolecules. To obtain optimal ECL-ET efficiency, perfect energy overlapped donor/acceptor pair is of great importance. Herein, we present a sensitive ECL-ET based immunosensor for the detection of tumor markers, using energy tunable CdSeTe/CdS/ZnS double shell quantum dots (QDs) and gold nanorods (GNRs) as the donor and acceptor, respectively. Firstly a facile microwave-assisted strategy for the synthesis of green- to near-infrared-emitting CdSeTe/CdS/ZnS QDs with time- and component-tunable photoluminescence was proposed. And, on the basis of the adjustable optical properties of both CdSeTe/CdS/ZnS QDs and GNRs, excellent overlap between donor emission and acceptor absorption can be obtained to ensure effective ECL-ET quenching, thus improving the sensing sensitivity. This method represents a novel approach for versatile detection of biomolecules at low concentrations.

N-acetylglucosamine biofunctionalized CdSeTe quantum dots as fluorescence probe for specific protein recognition.

Hsp70 proteins are implicated in resistance to chemotherapy in cancers, the detection of which is important for cancer treatment and prognosis. In this work, we report the study on the detection of specific intracellular target protein in fixed cells using GlcNAc-conjugated CdSeTe QDs. The QDs were coupled with Con A via a carbodiimide reaction and then were further assembled with GlcNAc by lectin-carbohydrate interaction between Con A and GlcNAc. The obtained QDs-Con A-GlcNAc conjugates have an emission wavelength at 650 nm that is close to the near-infrared (NIR) regions and a specific recognition for Hsp70. These results show that the QDs-Con A-GlcNAc probe can be a promising tool for direct localization of the Hsp70 protein.

Study on tumor microvasculature damage induced by alternate cooling and heating.

Tumor vasculature damage induced by various thermal treatments has been studied in vivo via laser confocal microscopy. Murine mammary carcinoma 4T1 was implanted in the nude mice dorsal skin fold window chamber. The implanted tumor was treated by alternate cooling and heating. Results showed that the treatment was much more effective as compared with that of cooling or heating alone, especially in damaging the tumor vasculature. In general, tumor vascular response to thermal stimuli was heterogeneous. All the treatments of hyperthermia at 42 degrees C (for 1 h), alternate cooling at 1 degrees C and heating at 42 degrees C (for 1/2 h each) and that of -10 degrees C/42 degrees C (for 1/2 h each) enhanced liposome extravasation. Pre-cooling tumor at 1 degrees C preserved most of the vascular integrity but partially inhibited the effect of post-hyperthermia at 42 degrees C. On the other hand, cooling at -10 degrees C for 1/2 h before heating at 42 degrees C caused severe vessel damage. Histo-pathological analyses further confirmed the effect as rare tumor vessel recurrence and large necrotic tumor tissue areas shown on the 7th day after the treatment.