pH/GSH dual-responsive nanoparticle for auto-amplified tumor therapy of breast cancer.

Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.

[Role of endoplasmic reticulum stress response in regulation of adipose tissue metabolism].

In eukaryotic cells, the endoplasmic reticulum (ER) is the key quality control organelle for cellular protein synthesis and processing. It also serves as an important site for Ca2+ storage and lipid biosynthesis. In response to a variety of external stimuli, a cellular unfolded protein response (UPR) is activated to handle ER stress caused by increased accumulation of unfolded or misfolded proteins at the ER. The UPR plays a crucial role in maintaining ER homeostasis and cell functions. Three ER-localized transmembrane proteins, inositol-requiring enzyme 1α (IRE1α), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6), act to sense ER stress and mediate three canonical UPR signaling pathways. Besides restoring the protein folding capability to relieve ER stress, the UPR pathways have also been implicated in the regulation of cell metabolism and energy balance. In the state of overnutrition, ER stress has been documented to occur in adipose tissue that has a key role in energy storage and consumption. As an endocrine organ, adipose tissue regulates glucose and lipid metabolism through secreting adipocyte cytokines, and it undergoes metabolic inflammation during pathogenic development of obesity, insulin resistance and type 2 diabetes. In this review, we attempt to summarize the recent progress with regard to the UPR regulation of adipose tissue physiology. We wish to focus upon the mechanism by which ER stress response is linked to adipose tissue dysfunction, hoping to promote our current understanding of UPR signaling in the pathophysiology of obesity and related metabolic diseases.

Reverse Multidrug Resistance in Human HepG2/ADR by Anti-miR-21 Combined with Hyperthermia Mediated by Functionalized Gold Nanocages.

Multidrug resistance (MDR) remains a formidable challenge to effective clinical cancer therapy. Herein, a nonviral gene delivery system HA/anti-miR-21/PPAuNCs to overcome MDR was reported. This system could condense the microRNA-21 inhibitor (anti-miR-21) into hyaluronic acid-conjugated and polyethylenimine-modified PEGylated gold nanocages (AuNCs) and had good stability. In vitro studies demonstrated that HA/anti-miR-21/PPAuNCs could enhance intracellular DOX accumulation in DOX-resistant HCC cells (HepG2/ADR cells) and increase the sensitivity to DOX of HepG2/ADR cells through upregulating PTEN protein expression mediated by anti-miR-21 and downregulating P-gp protein expression mediated by the hyperthermia of HA/PPAuNCs upon mild near-infrared irradiation. Furthermore, the therapeutic effects had been enhanced due to the combination of chemotherapy, gene therapy, and photothermal therapy. Besides, HA/anti-miR-21/PPAuNCs have a good biocompatibility. These findings can provide new insights and strategies for the treatment of cancers with MDR.

In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence.

Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.

Light-driven micro/nanomotors in biomedical applications.

Nanotechnology brings hope for targeted drug delivery. However, most current drug delivery systems use passive delivery strategies with limited therapeutic efficiency. Over the past two decades, research on micro/nanomotors (MNMs) has flourished in the biomedical field. Compared with other driven methods, light-driven MNMs have the advantages of being reversible, simple to control, clean, and efficient. Under light irradiation, the MNMs can overcome several barriers in the body and show great potential in the treatment of various diseases, such as tumors, and gastrointestinal, cardiovascular and cerebrovascular diseases. Herein, the classification and mechanism of light-driven MNMs are introduced briefly. Subsequently, the applications of light-driven MNMs in overcoming physiological and pathological barriers in the past five years are highlighted. Finally, the future prospects and challenges of light-driven MNMs are discussed as well. This review will provide inspiration and direction for light-driven MNMs to overcome biological barriers in vivo and promote the clinical application of light-driven MNMs in the biomedical field.

Red blood cell membrane-coated functionalized Au nanocage as a biomimetic platform for improved MicroRNA delivery in hepatocellular carcinoma.

Dysregulation of microRNAs (miRNAs) expression is closely related to cancers and managing miRNA expression holds great promise for cancer therapy. However, their wide clinical application has been hampered by their poor stability, short half-life and non-specific biodistribution in vivo. Herein, a novel biomimetic platform designated as RHAuNCs-miRNA for improved miRNA delivery was prepared through wrapping miRNA-loaded functionalized Au nanocages (AuNCs) with red blood cell (RBC) membrane. RHAuNCs-miRNA not only successfully loaded miRNAs but also effectively protected them from enzymatic degradation. With good stability, RHAuNCs-miRNA had the characteristics of photothermal conversion and sustained release. Cellular uptake of RHAuNCs-miRNA by SMMC-7721 cells was in a time-dependent manner via clathrin- and caveolin-mediated endocytosis. The uptake of RHAuNCs-miRNAs was affected by cell types and improved by mild near infrared (NIR) laser irradiation. More importantly, RHAuNCs-miRNA exhibited a prolonged circulation time without the occurrence of accelerated blood clearance (ABC) in vivo, resulting in efficient delivery to tumor tissues. This study may demonstrate the great potential of RHAuNCs-miRNA for improved miRNAs delivery.

Recent progress of micro/nanomotors to overcome physiological barriers in the gastrointestinal tract.

Oral administration is a convenient administration route for gastrointestinal disease therapy with good patient compliance. But the nonspecific distribution of the oral drugs may cause serious side effects. In recent years, oral drug delivery systems (ODDS) have been applied to deliver the drugs to the gastrointestinal disease sites with decreased side effects. However, the delivery efficiency of ODDS is tremendously limited by physiological barriers in the gastrointestinal sites, such as the long and complex gastrointestinal tract, mucus layer, and epithelial barrier. Micro/nanomotors (MNMs) are micro/nanoscale devices that transfer various energy sources into autonomous motion. The outstanding motion characteristics of MNMs inspired the development of targeted drug delivery, especially the oral drug delivery. However, a comprehensive review of oral MNMs for the gastrointestinal diseases therapy is still lacking. Herein, the physiological barriers of ODDS were comprehensively reviewed. Afterward, the applications of MNMs in ODDS for overcoming the physiological barriers in the past 5 years were highlighted. Finally, future perspectives and challenges of MNMs in ODDS are discussed as well. This review will provide inspiration and direction of MNMs for the therapy of gastrointestinal diseases, pushing forward the clinical application of MNMs in oral drug delivery.

Stimuli-Responsive Gold Nanocages for Cancer Diagnosis and Treatment.

With advances in nanotechnology, various new drug delivery systems (DDSs) have emerged and played a key role in the diagnosis and treatment of cancers. Over the last two decades, gold nanocages (AuNCs) have been attracting considerable attention because of their outstanding properties. This review summarizes current advancements in endogenous, exogenous, and dual/multi-stimuli responsive AuNCs in drug delivery. This review focuses on the properties, clinical translation potential, and limitations of stimuli-responsive AuNCs for cancer diagnosis and treatment.

Adipocyte IRE1α promotes PGC1α mRNA decay and restrains adaptive thermogenesis.

Adipose tissue undergoes thermogenic remodeling in response to thermal stress and metabolic cues, playing a crucial role in regulating energy expenditure and metabolic homeostasis. Endoplasmic reticulum (ER) stress is associated with adipose dysfunction in obesity and metabolic disease. It remains unclear, however, if ER stress-signaling in adipocytes mechanistically mediates dysregulation of thermogenic fat. Here we show that inositol-requiring enzyme 1α (IRE1α), a key ER stress sensor and signal transducer, acts in both white and beige adipocytes to impede beige fat activation. Ablation of adipocyte IRE1α promotes browning/beiging of subcutaneous white adipose tissue following cold exposure or ß3-adrenergic stimulation. Loss of IRE1α alleviates diet-induced obesity and augments the anti-obesity effect of pharmacologic ß3-adrenergic stimulation. Notably, IRE1α suppresses stimulated lipolysis and degrades Ppargc1a messenger RNA through its RNase activity to downregulate the thermogenic gene program. Hence, blocking IRE1α bears therapeutic potential in unlocking adipocytes' thermogenic capacity to combat obesity and metabolic disorders.

Cardioprotection of salvianolic acid B and ginsenoside Rg1 combination on subacute myocardial infarction and the underlying mechanism.

BACKGROUND: Following myocardial infarction (MI), a series of structural and functional changes evolves in the myocardium, collectively defined as cardiac remodeling. PURPOSE: The aim of present study was to investigate the cardioprotection of salvianolicacid B (SalB) and ginsenoside Rg1 (Rg1) combination against cardiac remodeling in a rat model at the subacute phase of MI and further elucidate the underlying mechanism. METHODS: Rat heart was exposed via a left thoracotomy at the fourth intercostal space and MI was induced by a ligature below the left descending coronary artery. Hemodynamic assay was conducted using a Mikro-tipped SPR-320 catheter which was inserted through the right carotid artery into left ventricle.Myocardial infarct size was detected using 3,5-triphenyltetrazolium chloride (TTC) staining. Haematoxylin and eosin (HE) stain and picric sirius red stain were conducted for histopathological detection. Immunohistochemistry was used to detect the expression of α-smooth muscle actin (α-SMA) and gelatin zymography was used to evaluate the activities of matrix metalloproteinase-9 (MMP-9). RESULTS: Comparing with MI rats, 30 mg/kg SalB-Rg1 improved cardiac function verified by maximum rate of pressure development for contraction (+dp/dtmax, p < 0.01) and maximum rate of pressure development for relaxation (-dp/dtmax, p < 0.05); reduced myocardial infarct size (p < 0.05) verified by TTC staining, improved cardiac structure based on HE stain; decreased collagen volume fraction (p < 0.05) and collagen I/III ratio (p < 0.05) according picrosirius red staining. The underlying mechanism of SalB-Rg1 against cardiac remodeling was associated with its down-regulation on α-SMA expression according immunohistochemistry (p < 0.01) and inhibition on MMP-9 activity based on in-gel zymography (p < 0.05). CONCLUSION: All above study indicated the potential therapeutic effects of SalB-Rg1 on heart.

PEGylated hyaluronidase/NIR induced drug controlled release system for synergetic chemo-photothermal therapy of hepatocellular carcinoma.

In recent years, cancer treatment has been facing the challenge of increasing antitumor efficiency and avoiding severe adverse effects simultaneously. In this study, we designed a controlled release drug delivery system, doxorubicin (Dox)-loaded and hyaluronic acid (HA)-modified PEGylated gold nanocages (AuNCs), which was designated as PEG-HAn-AuNCs/Dox (n represented 10n HA repeating units were modified on each AuNC). In this system, AuNCs were applied as the photothermal cores, Dox was employed as the model drug, HA was applied as the tumor-microenvironment responsive switch to achieve controlled release, and poly (ethylene glycol) (PEG) was used as the stealth polymer to prolong systemic circulation time. Firstly, we evaluated the physical and chemical properties of the PEG-HAn-AuNCs/Dox with different ratios of HA to AuNC and found that PEG-HA4-AuNCs/Dox was the optimal. Secondly, PEG-HA4-AuNCs/Dox revealed the feature of controlled release, namely, the drug release was triggered by hyaluronidase (HAase) and accelerated by the acidic pH and near-infrared (NIR) irradiation. And then PEG-HA4-AuNCs/Dox could be effectively delivered to a cultured SMMC-7721 cell line in vitro and the tumor tissues of the subcutaneous mouse models of hepatocellular carcinoma (HCC) in vivo. Finally, the results demonstrated the synergetic therapy, namely the combination of chemotherapy and photothermal therapy (PTT) (defined as chemo-photothermal therapy) mediated by PEG-HA4-AuNCs/Dox, could efficiently inhibit the tumor growth both in vitro and in vivo. Therefore, the advantages of PEG-HA4-AuNCs/Dox endowed it as a great potential candidate for HCC treatment.

Gene Therapy and Photothermal Therapy of Layer-by-Layer Assembled AuNCs /PEI/miRNA/ HA Nanocomplexes.

BACKGROUND: MicroRNA (miRNA) therapy, which was widely considered to treat a series of cancer, has been confronted with numerous obstacles to being delivered into target cells because of its easy biodegradation and instability. METHODS: In this research, we successfully constructed 11-mercaptoundecanoic acid modified gold nanocages (AuNCs)/polyethyleneimine (PEI)/miRNA/hyaluronic acid (HA) complexes (abbreviated as AuNCs/PEI/miRNA/HA) using a layer-by-layer method for target-specific intracellular delivery of miRNA by HA receptor mediated endocytosis. RESULTS: The results of UV spectra, hydrodynamic diameter and zeta potential analyses confirmed the formation of AuNCs/PEI/ miRNA/HA complex with its average particle size of ca. 153 nm and surface charge of ca. -9.43 mV. Next, we evaluated the antitumor effect of the nanocomplex mediated by the combination of gene therapy and photothermal therapy (PTT) against hepatocellular carcinoma (HCC) in vitro. CONCLUSION: Our experimental results indicated that the AuNCs/PEI/miRNA/HA complex effectively delivered miRNA to the target cells and its antitumor effect was significantly enhanced by the combination of gene therapy and photothermal therapy. In addition, anti-miR-181b could promote Bel-7402 cell arrest in S phase and improve TIMP-3 mRNA expression. All these results suggested that AuNCs/PEI/miRNA/HA gene delivery system with combination of gene therapy and photothermal therapy might be exploited for HCC treatment.

Triple therapy of hepatocellular carcinoma with microRNA-122 and doxorubicin co-loaded functionalized gold nanocages.

A combination of different therapy strategies has great potential to efficaciously treat malignant tumors, by virtue of their synergetic effects. Herein, a co-delivery system based on gold nanocages (AuNCs) was designed to deliver both doxorubicin (DOX) and microRNA-122 mimic (miR-122) for an enhanced cancer therapy. DOX was loaded into the AuNCs and miR-122 was condensed onto the surface of the functionalized AuNCs by an electrostatic interaction. Polyethyleneglycol (PEG) and hyaluronic acid (HA) were also introduced to the co-delivery system for targeted drug delivery. We evaluated the cellular uptake, biodistribution and anti-tumor effect in vitro and in vivo. Our results demonstrated an effective delivery of DOX and miR-122 into tumor cells and the tumor tissue. Importantly, the triple therapy, namely the combination of chemotherapy, gene therapy and photothermal therapy, mediated by this multifunctional drug delivery system, exhibited better anti-tumor effect than any single therapy, both in vitro and in vivo. Additionally, this drug delivery system caused insignificant toxicity to the major organs and had no obvious effect on the body weight of the mice. It could be concluded that multifunctional AuNCs are promising as a co-delivery vector for an enhanced anti-tumor effect.

Vitamin C and sodium bicarbonate enhance the antioxidant ability of H9C2 cells and induce HSPs to relieve heat stress.

Heat stress is exacerbated by global warming and affects human and animal health, leading to heart damage caused by imbalances in reactive oxygen species (ROS) and the antioxidant system, acid-base chemistry, electrolytes and respiratory alkalosis. Vitamin C scavenges excess ROS, and sodium bicarbonate maintains acid-base and electrolyte balance, and alleviates respiratory alkalosis. Herein, we explored the ability of vitamin C alone and in combination with equimolar sodium bicarbonate (Vitamin C-Na) to stimulate endogenous antioxidants and heat shock proteins (HSPs) to relieve heat stress in H9C2 cells. Control, vitamin C (20 µg/ml vitamin C for 16 h) and vitamin C-Na (20 µg/ml vitamin C-Na for 16 h) groups were heat-stressed for 1, 3 or 5 h. Granular and vacuolar degeneration, karyopyknosis and damage to nuclei and mitochondria were clearly reduced in treatment groups, as were apoptosis, lactate dehydrogenase activity and ROS and malondialdehyde levels, while superoxide dismutase activity was increased. Additionally, CRYAB, Hsp27, Hsp60 and Hsp70 mRNA levels were upregulated at 3 h (p < 0.01), and protein levels were increased for CRYAB at 0 h (p < 0.05) and 1 h (p < 0.01), and for Hsp70 at 3 and 5 h (p < 0.01). Thus, pre-treatment with vitamin C or vitamin C-Na might protect H9C2 cells against heat damage by enhancing the antioxidant ability and upregulating CRYAB and Hsp70.

Construction and application of a liver cancer-targeting drug delivery system based on core-shell gold nanocages.

BACKGROUND: In order to achieve drug targeting and controlled release, we have successfully developed a novel drug release system DOX/AuNCs-PM-HA with gold nanocages (AuNCs) as photothermal cores, thermally responsive copolymer P(NIPAM-co-Am) (PM) as the near-infrared (NIR) stimuli gatekeeper and hyaluronic acid as a targeting ligand as well as a capping agent. METHODS: Cell uptake and cell viability were investigated. In vivo photoacoustic tomography imaging in H22 tumor bearing mice was analyzed for the tumor targeting effect of the nanocomplexes. Antitumor efficacy and the tissue distribution in vivo were investigated. RESULTS: In vitro results demonstrated that the DOX/AuNCs-PM-HA had significant anticancer activity against SMMC-7721 cells under NIR irradiation. Furthermore, in vivo photoacoustic tomography imaging of the nanocomplexes in H22 tumor bearing mice could indicate effective tumor targeting. Our studies on antitumor efficacy and the tissue distribution in vivo showed that many DOX/AuNCs-PM-HA nanocomplexes could efficiently accumulate at the tumor site so that they could inhibit the tumor growth effectively with limited side effects. The in vitro and in vivo results confirmed that the tumor-targeting and controlled-release drug system DOX/AuNCs-PM-HA with the combination of chemotherapy and photothermal therapy showed strong anti-tumor effect and would have great potential for future cancer therapy. CONCLUSION: This tumor targeting DOX/AuNCs-PM-HA nanocomplex responded not only to the external stimuli of NIR, but also the internal stimuli of hyaluronidase, providing the potential for pinpointed and multi-stimuli responsive intracellular drug release.

Self-Regulated Carboxyphenylboronic Acid-Modified Mesoporous Silica Nanoparticles with "Touch Switch" Releasing Property for Insulin Delivery.

Glucose-responsive insulin delivery systems, which can maintain a stable level of blood glucose, have been proposed as a promising method to treat diabetes. Such systems can reduce potential toxicity and enhance patient compliance compared to traditional therapies. Accordingly, we designed a mesoporous silica nanoparticle (MSN)-based glucose-sensitive and self-regulated drug release system to achieve the goal of long circulation and "touch switch" in vivo. In this system, carboxyphenylboronic acid (CPBA) was first modified on the surface of MSN using amidation reaction. Insulin (INS) was then loaded in the channels of MSN (CPBA-MSN/INS) through physical adsorption, and sodium alginate (SA) was introduced onto the surface of the CPBA-MSN/INS nanoparticles as the gatekeeper via amidation reaction (SA/CPBA-MSN/INS). We found the drug loading capacity of INS was 261 mg/g. In the normal range of blood glucose, INS was scarcely released due to the reversible covalent interaction between 1,2-diols of SA and CPBA. Within the high concentration of glucose, the boronate esters could be dissociated, which results in the mesoporous channels opening and the release of INS. In vivo experiments on diabetic mice showed SA/CPBA-MSN/INS sustained a normal blood glucose level for up to 12 h with a single dose. Moreover, the lipid metabolism disorder and organ damage of diabetic mice were alleviated after treatment with SA/CPBA-MSN/INS. Therefore, SA/CPBA-MSN/INS characterized by an "on-off" regulated drug release property and high biosafety shows promise for applications in diabetes treatment.

Isolation and characterization of phosphofungi, and screening of their plant growth-promoting activities.

Rhizospheric microorganisms can increase phosphorus availability in the soil. In this regard, the ability of phosphofungi to dissolve insoluble phosphorus compounds is greater than that of phosphate-solubilizing bacteria. The aim of the current study was to identify efficient phosphofungi that could be developed as commercial microbial agents. Among several phosphate-solubilizing fungal isolates screened, strain CS-1 showed the highest phosphorus-solubilization ability. Based on phylogenetic analysis of the internal transcribed spacer region sequence, it was identified as Aspergillus niger. High-performance liquid chromatography analysis revealed that the mechanism of phosphorus solubilization by CS-1 involved the synthesis and secretion of organic acids, mainly oxalic, tartaric, and citric acids. Furthermore, strain CS-1 exhibited other growth-promoting abilities, including efficient potassium release and degradation of crop straw cellulose. These properties help to returning crop residues to the soil, thereby increasing nutrient availability and sustaining organic matter concentration therein. A pot experiment revealed that CS-1 apparently increased the assessed biometric parameters of wheat seedlings, implying the potential of this strain to be developed as a commercial microbial agent. We used Illumina MiSeq sequencing to investigate the microbial community composition in the rhizosphere of uninoculated wheat plants and wheat plants inoculated with the CS-1 strain to obtain insight into the effect of the CS-1 strain inoculation. The data clearly demonstrated that CS-1 significantly reduced the content of pathogenic fungi, including Gibberella, Fusarium, Monographella, Bipolaris, and Volutella, which cause soil-borne diseases in various crops. Strain CS-1 may hence be developed into a microbial agent for plant growth improvement.

A54 peptide-mediated functionalized gold nanocages for targeted delivery of DOX as a combinational photothermal-chemotherapy for liver cancer.

The combination of photothermal therapy and chemotherapy (photothermal-chemotherapy) is a promising strategy for cancer therapy. Gold nanocages (AuNCs), with hollow and porous structures and unique optical properties, have become a rising star in the field of drug delivery. Here, we designed a novel targeted drug delivery system based on functionalized AuNCs and evaluated their therapeutic effects in vitro and in vivo. We then loaded doxorubicin into this promising system, designated as DHTPAuNCs consisting of hyaluronic acid-grafted and A54 peptide-targeted PEGylated AuNCs. Its formation was corroborated by ultraviolet-visible spectroscopy, transmission electron microscopy and dynamic light scattering. This delivery platform needed hyaluronidase to release encapsulated drugs, meanwhile the acidic pH and near-infrared irradiation could accelerate the release. In addition, the results of cellular uptake demonstrate that this system could bind specifically with BEL-7402 cells. In vitro, we evaluated therapeutic effects of the DHTPAuNCs in BEL-7402 cells by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay. Moreover, in BEL-7402 tumor-bearing nude mice, its therapy effect in vivo was also evaluated. As expected, DHTPAuNCs exhibited excellent therapeutic effect by photothermal-chemotherapy, both in vitro and in vivo. In short, DHTPAuNCs with low toxicity showed great potential as a drug delivery system for cancer therapy.

Rapid determination of 30 bioactive constituents in XueBiJing injection using ultra high performance liquid chromatography-high resolution hybrid quadrupole-orbitrap mass spectrometry coupled with principal component analysis.

Xuebijing injection (XBJ) is a traditional Chinese herbal prescription widely used in the treatment of sepsis. Extensive chemical studies revealed that XBJ injection contains amino acids, phenolic acids, flavonoid glycosides, terpeneglycosides and phthalides. In this study, the applicability of ultra high performance liquid chromatography coupled with high resolution hybrid quadruple-orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS) for the simultaneous quantitative analysis of 30 bioactive constituents in XueBiJing injection (XBJ) was investigated. The mass spectrometer was operated in full MS scan mode. The use of 70,000FWHM mass resolution and narrow mass windows (5ppm) could effectively improve the selectivity of the method. Separation was achieved on a Waters ACQUITY UPLC® HSS C18 column (2.1mm×100mm, 1.8µm) with a gradient mobile phase consisting of acetonitrile-water (containing 10mM ammonium acetate) at a flow rate of 0.2mL/min. Satisfactory linearity was achieved within wide linear range and all correlation coefficients (r) of analytes were more than 0.9996. The limits of detection (LODs) were in the range of 0.1180-27.82ng/mL for different analytes. The relative standard deviations (RSDs) of inter- and intra-day precisions were less than 3.0% and the recoveries of the assay were in the range of 98.5%-101.5%. The validated method was successfully applied for simultaneous determination of 30 bioactive compounds in XueBiJing injection from 10 batches samples by UHPLC-Q-Orbitrap MS within 10min. Moreover, the results were evaluated principal component analysis and two compounds might be the most important chemical markers for chemical quality control of XBJ injection. The novel Q-Orbitrap mass spectrometry has been proved to be a very promising and powerful tool for routine screening of bioactive compounds in traditional Chinese medicine injection, ensuring drug safety and public health.

Gold nanocages with dual modality for image-guided therapeutics.

Numerous studies have demonstrated that microRNAs are very important in cancer development and progression. However, the complex relationship between the size of microRNA delivery systems, cellular uptake, biodistribution and therapeutic efficiency remains unclear. Herein, we have successfully constructed a series of differently-sized microRNA delivery systems, miR-26a-loaded, hyaluronic acid-modified, polyetherimide-conjugated PEGylated gold nanocage ternary nanocomplexes (PPHAuNCs-TNCs), which can be monitored optically by fluorescence and photoacoustic tomography imaging. We evaluated the effect of the particle size on the cellular uptake and biodistribution in the BEL-7402 cell line in vitro and in the subcutaneous and orthotopic hepatocellular carcinoma (HCC) mouse models. Our findings showed that the cellular uptake and biodistribution were optimal for cancer therapy with the PPHAuNCs-30-TNCs (30 nm AuNCs in edge length) in comparison with their 50 nm and 70 nm counterparts. PPHAuNCs-30-TNCs could accumulate in the liver for a longer time in an orthotopic mouse model of HCC than that in normal mice and could considerably restrain tumor growth in an orthotopic HCC mouse model under near-infrared radiation. This study may provide insightful information for developing novel non-viral microRNA vectors, and PPHAuNCs-30-TNCs have great potential for application in tumor diagnosis and cancer therapy in the future.