The Graphene Quantum Dots Gated Nanoplatform for Photothermal-Enhanced Synergetic Tumor Therapy.

Currently, the obvious side effects of anti-tumor drugs, premature drug release, and low tumor penetration of nanoparticles have largely reduced the therapeutic effects of chemotherapy. A drug delivery vehicle (MCN-SS-GQDs) was designed innovatively. For this, the mesoporous carbon nanoparticles (MCN) with the capabilities of superior photothermal conversion efficiency and high loading efficiency were used as the skeleton structure, and graphene quantum dots (GQDs) were gated on the mesopores via disulfide bonds. The doxorubicin (DOX) was used to evaluate the pH-, GSH-, and NIR-responsive release performances of DOX/MCN-SS-GQDs. The disulfide bonds of MCN-SS-GQDs can be ruptured under high glutathione concentration in the tumor microenvironment, inducing the responsive release of DOX and the detachment of GQDs. The local temperature of a tumor increases significantly through the photothermal conversion of double carbon materials (MCN and GQDs) under near-infrared light irradiation. Local hyperthermia can promote tumor cell apoptosis, accelerate the release of drugs, and increase the sensitivity of tumor cells to chemotherapy, thus increasing treatment effect. At the same time, the detached GQDs can take advantage of their extremely small size (5-10 nm) to penetrate deeply into tumor tissues, solving the problem of low permeability of traditional nanoparticles. By utilizing the photothermal properties of GQDs, synergistic photothermal conversion between GQDs and MCN was realized for the purpose of synergistic photothermal treatment of superficial and deep tumor tissues.

Combination immunotherapy of PEG-modified preladenant thermosensitive liposomes and PD-1 inhibitor effectively enhances the anti-tumor immune response and therapeutic effects.

Immunotherapy is a promising cancer treatment strategy. In contrast, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors are associated with low response rates and are only useful in a small group of cancer patients. A combination of treatments may be effective for overcoming this clinical issue. Preladenant is an adenosine (ADO) receptor inhibitor that can block the ADO pathway and improve the tumor microenvironment (TME), thereby enhancing the immunotherapeutic effect of PD-1 inhibitors. However, its poor water solubility and low targeting limit its clinical applications. We designed a PEG-modified thermosensitive-liposome (pTSL) loaded with ADO small molecule inhibitor preladenant (P-pTSL) to overcome these problems and enhance the effect of PD-1 inhibitor on breast cancer immunotherapy. The prepared P-pTSL was round and uniformly distributed with a particle size of (138.9 ± 1.22) nm, PDI: 0.134 ± 0.031, and zeta potential (-10.1 ± 1.63) mV; preladenant was released slowly at 37 °C but released fast at 42 °C from P-pTSL, which was 76.52 ± 0.44%. P-pTSL has good long-term and serum stability and excellent tumor-targeting ability in mice. Moreover, the combination with PD-1 inhibitor significantly enhanced the anti-tumor effect, and the improvement of related factors in serum and lymph was more obvious under the condition of 42 °C thermotherapy in vitro.

Customized multi-stimuli nanovehicles with dissociable 'bomblets' for photothermal-enhanced synergetic tumor therapy.

Recently, the therapeutic effect of chemotherapy has been obviously impaired due to premature drug release, low tumor penetration, and multidrug resistance of nanoplatforms. In this paper, a novel multiple-sensitive drug delivery system (MC-ss-CDs) was developed by gating long-wavelength emitting carbon dots (CDs) on the openings of mesoporous carbon nanoparticles (MC) through disulfide bonds. The MC with excellent photothermal transition efficiency and high drug storage capacity for doxorubicin (DOX) was used as the delivery carrier. The CDs had multiple functions, including intelligent switching to hinder unwanted release, photothermal therapy (PTT) agents to improve the heat generation effect of MCs and bioimaging trackers to monitor drug delivery. The disulfide bonds, as the linkers between MC carriers and CDs, are stable under normal physical conditions and relatively labile under high GSH concentrations in the cytoplasm of tumor cells. After arriving at the tumor microenvironment, DOX/MC-ss-CDs can rapidly break into DOX/MC and CDs under high GSH concentrations. DOX/MC could realize efficient integration of PTT and chemotherapy on the surface of the tumor by stimuli-responsive DOX release and synergetic heating of MC and CDs. The small-sized CDs with excellent penetrating ability could effectively enter the deep tumor and realize NIR-triggered photothermal ablation. The DOX/MC-ss-CDs showed a chemophotothermal effect with a combination index of 0.38 in vitro and in vivo. Therefore, the DOX/MC-ss-CDs could be employed as a trackable nanovehicle for synergistic chemotherapy and PTT at different depths.

Biomimetic Antidote Nanoparticles: a Novel Strategy for Chronic Heavy Metal Poisoning.

Chronic lead poisoning has become a major factor in global public health. Chelation therapy is usually used to manage lead poisoning. Dimercaptosuccinic acid (DMSA) is a widely used heavy metal chelation agent. However, DMSA has the characteristics of poor water solubility, low oral bioavailability, and short half-life, which limit its clinical application. Herein, a long-cycle slow-release nanodrug delivery system was constructed. We successfully coated the red blood cell membrane (RBCM) onto the surface of dimercaptosuccinic acid polylactic acid glycolic acid copolymer (PLGA) nanoparticles (RBCM-DMSA-NPs), which have a long cycle and detoxification capabilities. The NPs were characterized and observed by particle size meters and transmission electron microscopy. The results showed that the particle size of RBCM-DMSA-NPs was approximately 146.66 ± 2.41 nm, and the zeta potential was - 15.34 ± 1.60 mV. The homogeneous spherical shape and clear core-shell structure of the bionic nanoparticles were observed by transmission electron microscopy. In the animal tests, the area under the administration time curve of RBCM-DMSA-NPs was 156.52 ± 2.63 (mg/L·h), which was 5.21-fold and 2.36-fold that of free DMSA and DMSA-NPs, respectively. Furthermore, the median survival of the RBCM-DMSA-NP treatment group (47 days) was 3.61-fold, 1.32-fold, and 1.16-fold for the lead poisoning group, free DMSA, and DMSA-NP groups, respectively. The RBCM-DMSA-NP treatment significantly extended the cycle time of the drug in the body and improved the survival rate of mice with chronic lead poisoning. Histological analyses showed that RBCM-DMSA-NPs did not cause significant systemic toxicity. These results indicated that RBCM-DMSA-NPs could be a potential candidate for long-term chronic lead exposure treatment.

Novel biomimetic nanostructured lipid carriers for cancer therapy: preparation, characterization, and in vitro/in vivo evaluation.

Nanostructured lipid carriers (NLC) have become a research hotspot, wherein cancer-targeting effects are enhanced and side effects of chemotherapy are overcome. Usually, accelerated blood clearance (ABC) occurs after repeated injections, without changing the immunologic profile, despite PEGylation which prolongs the circulation function. To overcome these problems, we designed a red blood cell-membrane-coated NLC (RBCm-NLC), which was round-like, with a particle size of 60.33 ± 3.04 nm and a core-shell structure. Its stability was good, the drug paclitaxel (PTX) release from RBCm-PTX-NLC was less than 30% at pH7.4 and pH6.5, and the integrity of RBC membrane surface protein was maintained before and after preparation. Additionally, in vitro assays showed that, with the RBCm coating, the cellular uptake of the NLC by cancer cells was significantly enhanced. RBCm-NLC can avoid recognition by macrophage cells and prolong circulation time in vivo. In S180 tumor-bearing mice, the DiR-labeled RBCm-NLC group showed a stronger fluorescence signal and longer retention in tumor tissues, indicating a prompt tumor-targeting effect and extended blood circulation. Importantly, RBCm-PTX-NLC enhanced the antitumor effect and extended the survival period significantly in vivo. In summary, biomimetic NLC offered a novel strategy for drug delivery in cancer therapy.

Cancer cell membrane-coated mesoporous silica loaded with superparamagnetic ferroferric oxide and Paclitaxel for the combination of Chemo/Magnetocaloric therapy on MDA-MB-231 cells.

To effectively inhibit the growth of breast cancer cells (MDA-MB-231 cells) by the combination method of chemotherapy and magnetic hyperthermia, we fabricated a biomimetic drug delivery (CSiFePNs) system composed of mesoporous silica nanoparticles (MSNs) containing superparamagnetic ferroferric oxide and Paclitaxel (PTX) coated with MDA-MB-231 cell membranes (CMs). In the in vitro cytotoxicity tests, the MDA-MB-231 cells incubated with CSiFePNs obtained IC50 value of 0.8 µgL-1, 3.5-fold higher than that of SiFePNs. The combination method of chemotherapy and magnetic hyperthermia can effectively inhibit the growth of MDA-MB-231 cells.

Development of a matrix solid-phase dispersion extraction combined with high-performance liquid chromatography for determination of five lignans from the Schisandra chinensis.

A method based on a simplified sample extraction by matrix solid phase dispersion (MSPD) followed by HPLC determination is validated for analysis of five lignans in Schisandra chinensis. The MSPD parameters that affect the extraction efficiency of lignans from S. chinensis were examined and optimized. The optimal extraction conditions were determined to be that silica gel was used as dispersing sorbent, the ratio of silica gel to sample mass was selected to be 2:1, and 4mL of methanol was used as elution solvent. The method recoveries were determined to be from 92.25 to 101.17% and the RSDs from 1.3 to 4.9%. The extraction yields of five lignans obtained by the MSPD were higher than those of traditional reflux and sonication extraction with reduced requirements on sample, solvent and time. In addition, the optimized method was applied for analyzing five real S. chinensis samples obtained from different cultivated areas.

[Effects of Prostate Water Pellets on the number of colonies, NO concentration and NOS activity in the prostate tissue of CBP rats].

OBJECTIVE: To investigate the effects of Prostate Water Pellets (PWP) on the number of colonies, NO concentration and NOS activity in the prostate tissues of rats with chronic bacterial prostatitis (CBP). METHODS: A total of 120 healthy adult male Wistar rats weighing 250-300 g were equally randomized into 6 groups: blank control, model control, positive control, high-dose PWP, medium-dose PWP and low-dose PWP. The CBP rat models were established by injecting colibacilli (10(7)/ml) into the prostate. A month later, the high- , medium- and low-dose PWP groups were treated intragastrically with PWP at 4.4 g/kg, 2.2 g/kg and 1.1 g/kg per day respectively, the positive controls with levofloxacin at 0.018 g/kg per day, and the blank and model controls with normal saline, all for 35 days. Then the numbers of colonies in the prostate tissues were measured, and the changes in NO concentration and NOS activity detected by the nitrite reductase method. RESULTS: Compared with the model controls, the number of colonies, NO concentration and NOS activity were significantly reduced in the prostate tissues of the rats of the high- , medium- and low-dose PWP groups (P < 0.01). CONCLUSION: PWP was proved to be efficacious for CBP in rats, whose mechanism might be related with its inhibitory effect on bacterial growth and decreasing effect on NO concentration and NOS activity in the prostate tissues.

[Establish remote of sensing monitoring method and standard on wild rare medical plant].

At present the shortage of the resources of wild and rare medicinal plants is very serious in China. So grasping the situation and change tendency of medicinal plant resources comprehensive and real-timely, is vital significance to realize the sustainable using of medicinal plant resources. In order to use the remote sensing monitor technology and method to study the resources of the wild and rare medicinal plants, this article discusses the principle, method, technology and the principle and standard based on the operation and experiment of remote sensing monitor on the resources of wild rare medicinal plant.

[Analysis in distribution of Atractylodes lancea at Maoshan regions].

OBJECTIVE: To Investigate the distribution of Atractylodes lancea at Maoshan regions. METHODS: To combine the plot sampling with GIS technology in the analysis of distribution and its factors. RESULTS: The biomass of Atractylodes lancea was related to the growth of Ouercus serrata var. brevipetiolata, slope and humidity. The distribution of Atractylodes lancea which was less in north Maoshen region, most in south region, least in middle region. CONCLUSION: The main factor of distributing sintuation is the human beings. The leading factors in the biomass of Atractylodes lancea are Ouercus serrata var. brevipetiolata and slope.

[Biomass structure analysis of Atractylodes lancea in different ecological environments].

OBJECTIVE: To study the ecological environments of Atractylodes lancea by biomass structural analysis. METHOD: Through the scientific investigation in Maoshan, the sampling spots were set up, the relation between growth and ecological environments was researched and the ecological environments of A. lancea were divided as following: the vegetation layer, the shrub layer, the shrub-weed layer and the weed layer. The ramet biomass, height, leaves and coverage of A. lancea were studied. RESULT: The several factors (ramet biomass, height, leaves and coverage) showed the regular change. Among maximum, minimum and average, the shrub layer was the biggest, the shrub and weed layer was the second biggest and the vegetation layer and the weed layer was the least. CONCLUSION: A. lancea tends to distribute in the shrub layer and the shrub-weed layer.

[Comparing of different methods on habitat adaptive division of Chinese material medica].

OBJECTIVE: To comparing two kinds habitat adaptive division of Chinese material medica with different models. METHOD: The habitat adaptive divisions of A. lancea according essential oil accumulation with two kinds pattern, model pattern and template pattern were carrid and compared. RESULT: Two habitat adaptive divisions of A. lancea maps according essential oil accumulation were gotten. CONCLUSION: Both model pattern and template pattern were efficient on habitat adaptive division of Chinese material medica, but they shoud bu used with different processesd and based different background [corrected]

[Remote sensing resource monitoring on Atractylodes lancea].

Remote sensing technology was used for investigation of the resources of Atractylodes lancea. Firstly, the general situation of Jiangshu Maoshan and A. lancea in Maoshan was introduced; Secondly, the methods of remote sensing on the resource of the wild drugs were explained. Thirdly, the TM images were interpret according to the differences of the objects reflex spectrum, and growth environments in Damao mountain, Ermao mountain and Xiaomao mountain were divided into different sub-areas according to the results of the field investigations. Finally, the resource of A. lancea in Jiangshu Maoshan was estimated.

[Study on dynamical changes of Ginkgo biloba resources in Pizhou city of Jiangsu Province base on RS and GIS].

OBJECTIVE: To analyse the dynamical changes of the Ginkgo biloba's resources from 2001 to 2006, in Pizhou city, Jiangshu province by useing spatial analytical function of GIS and RS technology. METHOD: Use the GIS and RS technology, extracted the information of G. biloba by scientific investigation, researched the spatial distribution and dynamical changes of G. biloba based on landsat 5 TM: the Apr. 3rd, 2001; Jan. 16th, 2005; July 30th, 2006. RESULT: Ginkgo biloba's resource was 1.61 x 10(5) hm2 in 2001, 1.84 x 10(5) hm2 in 2005, 1.88 x 10(5) hm2 in 2006. CONCLUSION: Ginkgo biloba's resource rised from 1.61 x 10(5) hm2 to 1.88 x 10(5) hm2 from 2001 to 2006, showed the gradually rise.

[Remote sensing monitoring methods for medicinal plants resource in different types of ecological environment].

Different remote sensing monitoring methods are needed for the medicinal plant resource in different types of ecological environment. This paper explained remote sensing monitoring methods for the resource of the wild medicinal plants and cultivated plants, and analyzed the rare species, generous species and species in special ecological environment in detail. It provides a new method to all kind of medicinal plants resources' remote sensing monitoring.