Cyanobacterial Ampholyte Hydrogels Developed by the Cationization of Sulfated Polysaccharides and Their Cell-Compatibility.

Sacran is a cyanobacterial supergiant polysaccharide with carboxylate and sulfate groups that exhibits antiallergic and antiinflammatory properties. However, its high anionic functions restrict cell compatibility. Quaternary ammonium groups were substituted to form sacran ampholytes, and the cell compatibility of the cationized sacran hydrogels was evaluated. The cationization process involved the reaction of N-(3-chloro-2-hydroxypropyl)trimethylammonium chloride with the primary amine or hydroxyl groups of sacran. The degree of cationization ranged from 32 to 87% for sugar residues. Hydrogels of sacran ampholytes were prepared by annealing their dried sheets by thermal cross-linking; these hydrogels exhibited anisotropic expansion properties. The water contact angle on the hydrogels decreased from 26.5 to 15.3° with an increase in the degree of cationization, thereby enhancing hydrophilicity. The IC50 values of sacran ampholytes decreased with an increased degree of cationization, resulting in a reduction in cytotoxicity toward the L-929 mouse fibroblast cell line. This reduction was associated with an increase in the cell proliferation density after 3 days of incubation. Scanning electron microscopy images showed fibroblast intercellular connections. Therefore, the sacran ampholyte hydrogel exhibited increased hydrophilicity and cell compatibility, which is beneficial for various biomedical applications.

Water-soluble microencapsulation using gum Arabic and skim milk enhances viability and efficacy of Pediococcus acidilactici probiotic strains for application in broiler chickens.

OBJECTIVE: This study aimed to develop and evaluate the effectiveness of a water-soluble microencapsulation method for probiotic strains using gum Arabic (GA) and skim milk (SKM) over a three-month storage period following processing. METHODS: Four strains of Pediococcus acidilactici (BYF26, BYF20, BF9, and BF14) that were typical lactic acid bacteria (LAB) isolated from the chicken gut were mixed with different ratios of GA and SKM as coating agents before spray drying at an inlet temperature 140°C. After processing, the survivability and probiotic qualities of the strains were assessed from two weeks to three months of storage at varied temperatures, and de-encapsulation was performed to confirm the soluble properties. Finally, the antibacterial activity of the probiotics was assessed under simulated gastrointestinal conditions. RESULTS: As shown by scanning electron microscopy, spray-drying produced a spherical, white-yellow powder. The encapsulation efficacy (percent) was greatest for a coating containing a combination of 30% gum Arabic: 30% skim milk (w/v) (GA:SKM30) compared to lower concentrations of the two ingredients (p<0.05). Coating with GA:SKM30 (w/v) significantly enhanced (p<0.05) BYF26 survival under simulated gastrointestinal conditions (pH 2.5 to 3) and maintained higher survival rates compared to non-encapsulated cells under an artificial intestinal juices condition of pH 6. De-encapsulation tests indicated that the encapsulated powder dissolved in water while keeping viable cell counts within the effective range of 106 for 6 hours. In addition, following three months storage at 4°C, microencapsulation of BYF26 in GA:SKM30 maintained both the number of viable cells (p<0.05) and the preparation's antibacterial efficacy against pathogenic bacteria, specifically strains of Salmonella. CONCLUSION: Our prototype water-soluble probiotic microencapsulation GA:SKM30 effectively maintains LAB characteristics and survival rates, demonstrating its potential for use in preserving probiotic strains that can be used in chickens and potentially in other livestock.

Toxic Ag+ detection based on Au@Ag core shell nanostructure formation using Tannic acid assisted synthesis of Pullulan stabilized gold nanoparticles.

Herein, a sensitive colorimetric detection strategy is proposed for Ag+ detection based on the use of environmentally friendly synthesis of gold nanoparticles (AuNPs), at room temperature, using (tannic acid, TA), as the reductant and pullulan (PUL) as stabilizing agent. The colloidal solution (TA/PUL-AuNPs), at the optimal synthesis conditions, showed maximum absorbance at 529 nm with a berry red color. TEM and FESEM validated that the particles are spherical and monodispersed, while other characterization results elucidated the role of pullulan in the nano-synthesis. Ag+ addition to the probe (TA/PUL-AuNPs), pH 11, resulted in naked-eye color changes, owing to Au@Ag core shell nanostructure formation. Further, the added Ag+ is reduced to AgNPs, on the surface of the TA/PUL-AuNPs probe. A hypsochromic shift in the absorption maximum, from 529 to 409 nm was observed, while (AAg+-Abl)@409 nm exhibited linearity with Ag+ concentrations, from 0.100 to 150 µM. The estimated limit of detection was 30.8 nM, which is far lower than the acceptable limit of 0.930 µM from the regulatory agency. The TA/PUL-AuNPs probe was further tested for Ag+ detection in lake water samples, and it displayed satisfactory detection performances for real sample applications.

Research on Shelf-Life Extension Technologies for Food Sustainability: An Assessment of Scientific Activities and Networks.

A clearer understanding of research streams and players involved in efforts to address the sustainability of global food and agricultural systems is needed to clarify the current state of scientific knowledge and form collaborations to pursue future research directions. This study presents new insights into this issue through a scientometric process involving a case study of technologies for extending fruit shelf-life. The text mining software was utilized to analyze 3,131 Web of Science-indexed articles published between 2000 and 2020 as a means to glean the conceptual structure of current knowledge and conduct a social network analysis to explore scientific and publication activity. The findings were mapped onto a strategic diagram of research productivity and collaboration between players at the national, organizational, and individual levels. This research's main findings highlight that research on shelf-life technology is in continuous development, and academic institutions from China, Spain, and the U.S. are the core national players in this field. The results provide insights for further investigation to strengthen co-research and technological development programs in other fields. Researchers who are exploring networking opportunities can use the model and process presented as a guideline for identifying emerging and future research trends and formulating strategies.

Microencapsulated probiotic Lactiplantibacillus plantarum and/or Pediococcus acidilactici strains ameliorate diarrhoea in piglets challenged with enterotoxigenic Escherichia coli.

Lactiplantibacillus plantarum (strains 22F and 25F) and Pediococcus acidilactici (strain 72N) have displayed antibacterial activity in vitro, suggesting that they could be used to support intestinal health in pigs. The aim of this study was to determine if microencapsulated probiotics could reduce the severity of infection with enterotoxigenic Escherichia coli (ETEC) in weaned pigs. Sixty healthy neonatal piglets were cross-fostered and separated into five groups. Piglets to be given the microencapsulated probiotics received these orally on days 0, 3, 6, 9, and 12. Only piglets in groups 1 and 5 did not receive probiotics: those in groups 2 and 4 received the three microencapsulated probiotic strains (multi-strain probiotic), and piglets in group 3 received microencapsulated P. acidilactici strain 72N. After weaning, the pigs in groups 3-5 were challenged with 5 mL (at 109 CFU/mL) of pathogenic ETEC strain L3.2 carrying the k88, staP, and stb virulence genes. The multi-strain probiotic enhanced the average daily gain (ADG) and feed conversion ratio (FCR) of weaned piglets after the ETEC challenge (group 4), whilst supplementing with the single-strain probiotic increased FCR (group 3). Piglets in groups 3 and 4 developed mild to moderate diarrhoea and fever. In the probiotic-fed piglets there was an increase in lactic acid bacteria count and a decrease in E. coli count in the faeces. By using real-time PCR, virulence genes were detected at lower levels in the faeces of pigs that had received the probiotic strains. Using the MILLIPLEX MAP assay, probiotic supplementation was shown to reduce pro-inflammatory cytokines (IL-1α, IL-6, IL-8, and TNFα), while group 4 had high levels of anti-inflammatory cytokine (IL-10). Challenged piglets receiving probiotics had milder intestinal lesions with better morphology, including greater villous heights and villous height per crypt depth ratios, than pigs just receiving ETEC. In conclusion, prophylactic administration of microencapsulated probiotic strains may improve outcomes in weaned pigs with colibacillosis.

A novel modified chitosan/collagen coated-gold nanoparticles for 5-fluorouracil delivery: Synthesis, characterization, in vitro drug release studies, anti-inflammatory activity and in vitro cytotoxicity assay.

We report herein the development of the novel nanohybrids of gold nanoparticles reduced/stabilized/coated with collagen (AuNPs@collagen) in the first layer and subsequently modified with biotin-quat188-chitosan (Bi-QCS) in the outer layer for 5-fluorouracil (5-FU) delivery to improve cellular uptake and promote specific cell targeting of the nanocarrier. The fabrication of the layer-by-layer technique on the surface of gold nanoparticles (AuNPs) can overcome the limitation of poor drug loading capacity of the classic AuNPs from 64.67% to 87.46%. The AuNPs@collagen coated by the Bi-QCS exhibits strong electrostatic interactions between drug anion (5-FU) and amine groups of the modified chitosan as well as hydrogen bonding. Furthermore, the Bi-QCS-AuNPs@collagen demonstrated a significantly higher anti-inflammatory activity in RAW264.7 macrophage cell line. The Bi-QCS-AuNPs@collagen enhanced the activity of 5-FU approximately 3.3-fold (HeLa) and 6.2-fold (A549), compared to the free 5-Fluorouracil. According to these results, it is very promising that Bi-QCS-AuNPs@collagen can be used as an effective drug delivery carrier in the future.

Collaboration Network and Trends of Global Coronavirus Disease Research: A Scientometric Analysis.

As a global pandemic threatens health and livelihoods, finding effective treatments has become a vital issue that requires worldwide collaboration. This study examines research collaboration and network profiles through a case study of coronavirus diseases, including both the extinct severe acute respiratory syndrome coronavirus (SARS-CoV) and the emerging species (SARS-CoV-2). A scientometric process was designed to apply quantitative tools and a qualitative approach employing technological expertise to accomplish a three-level collaboration analysis. The text mining software, VantagePoint, was used to analyze research articles from the Web of Science database to identify the key national, organizational, and individual players in the coronavirus research field combined with indicators, namely, the breadth and depth of collaboration. The results show that China and the United States are at the center of coronavirus research networks at all three levels, including many endeavors involving single or joint entities. This study demonstrates how governments, public sectors, and private sectors, such as the pharmaceutical industry, can use scientometric analysis to gain insight into the holistic research trends and networks of players in this field, leading to the formulation of strategies to strengthen research and development programs. Furthermore, this approach can be utilized as a visualization and decision support tool for further policy planning, identification and execution of collaboration, and research exchange opportunities. This scientometric process should be directly applicable to other fields.

Enhancement of large ring cyclodextrin production using pretreated starch by glycogen debranching enzyme from Corynebacterium glutamicum.

Synthesis of large-ring cyclodextrins (LR-CDs) in any significant amount has been challenging. This study enhanced the LR-CDs production by Thermus filiformis amylomaltase (TfAM) enzyme by starch pretreatment using glycogen debranching enzyme from Corynebacterium glutamicum (CgGDE). CgGDE pretreated tapioca starch gave LR-CD conversion of 31.2 ± 2.2%, compared with LR-CDs produced from non-treated tapioca starch (16.0 ± 2.4%). CgGDE pretreatment enhanced amylose content by approximately 30%. Notably, a shorter incubation time of 1 h is sufficient for CgGDE starch pretreatment to produce high LR-CD yield, compared with 6 h required for the commercial isoamylase. High-Performance Anion Exchange Chromatography coupled with Pulsed Amperometric Detection (HPAEC-PAD) and Gel Permeable Chromatography (GPC) revealed that CgGDE is more efficient than the commercial isoamylase in debranching tapioca starch and gave lower molecular weight products. In addition, lower amount of by-products (linear oligosaccharides) were detected in cyclization reaction when using CgGDE-pretreated starch. In conclusion, CgGDE is a highly effective enzyme to promote LR-CD synthesis from starch with a shorter incubation time than the commercial isoamylase.

Targeted Gold Nanohybrids Functionalized with Folate-Hydrophobic-Quaternized Pullulan Delivering Camptothecin for Enhancing Hydrophobic Anticancer Drug Efficacy.

This study presented a green, facile and efficient approach for a new combination of targeted gold nanohybrids functionalized with folate-hydrophobic-quaternized pullulan delivering hydrophobic camptothecin (CPT-GNHs@FHQ-PUL) to enhance the efficacy, selectivity, and safety of these systems. New formulations of spherical CPT-GNHs@FHQ-PUL obtained by bio-inspired strategy were fully characterized by TEM, EDS, DLS, zeta-potential, UV-vis, XRD, and ATR-FTIR analyses, showing a homogeneous particles size with an average size of approximately 10.97 ± 2.29 nm. CPT was successfully loaded on multifunctional GNHs@FHQ-PUL via intermolecular interactions. Moreover, pH-responsive CPT release from newly formulated-CPT-GNHs@FHQ-PUL exhibited a faster release rate under acidic conditions. The intelligent CPT-GNHs@FHQ-PUL (IC50 = 6.2 µM) displayed a 2.82-time higher cytotoxicity against human lung cancer cells (Chago-k1) than CPT alone (IC50 = 2.2 µM), while simultaneously exhibiting less toxicity toward normal human lung cells (Wi-38). These systems also showed specific uptake by folate receptor-mediated endocytosis, exhibited excellent anticancer activity, induced the death of cells by increasing apoptosis pathway (13.97%), and arrested the cell cycle at the G0-G1 phase. The results of this study showed that the delivery of CPT by smart GNHs@FHQ-PUL systems proved to be a promising strategy for increasing its chemotherapeutic effects.

Solubility enhancement of poorly water soluble domperidone by complexation with the large ring cyclodextrin.

The water solubility of domperidone (DMP) could be improved by complexation with large ring cyclodextrins (LR-CDs). LR-CDs contain a relatively hydrophobic cavity that is capable of entrapping the molecules to form inclusion complexes. The complex formation capability of mixture LR-CDs having a degree of polymerization (DP) of 22-48, with DMP was investigated. The phase solubility profile of mixture LR-CD/DMP was classified as AN-type, resulting in increased DMP solubility in water by 3-fold. Various physicochemical techniques confirmed the mixture LR-CD/DMP complex formation. Single LR-CD with DP of 26, 27, 28, 29, 30, 33 and 34 (CD26 ~ CD34) were isolated from LR-CD mixtures using ODS column for HPLC separation. The CD33/DMP complex has demonstrated the most significant improvement compared to other single LR-CD complexes with a 2.7-fold increase in DMP solubility. The molecular dynamic result revealed that DMP formed stable complexes with CD33 by positioned fully encapsulated inside the cavity and covered by 13-14 subunits of CD33.

The efficacy of three double-microencapsulation methods for preservation of probiotic bacteria.

Lactic acid bacteria (LAB) are used as a probiotic alternative to antibiotics in livestock production. Microencapsulation technology is widely used for probiotic preservation. A variety of microencapsulation protocols have been proposed and compared based on chemicals and mechanical procedures. This study aimed to develop a double-encapsulated coating from alginate (1.5%) and chitosan (0.5%) by extrusion, emulsion, and spray drying methods using the LAB strains Lactobacillus plantarum strains 31F, 25F, 22F, Pediococcus pentosaceus 77F, and P. acidilactici 72N, and to monitor the basic probiotic properties of the encapsulated prototypes. The final products from each microencapsulation protocol were analysed for their appearance, probiotic properties and viable cell count. Using the spray drying method, particles smaller than 15 µm in diameter with a regular spherical shape were obtained, whereas the other methods produced larger (1.4-52 mm) and irregularly shaped microcapsules. After storage for 6 months at room temperature, the LAB viability of the spray-dried particles was the highest among the three methods. In all the LAB strains examined, the encapsulated LAB retained their probiotic properties in relation to acid-bile tolerance and antibacterial activity. This study highlights the efficacy of double-coating microencapsulation for preserving LAB properties and survival rate, and demonstrates its potential for probiotic application in livestock farms.

New organic/inorganic nanohybrids of targeted pullulan derivative/gold nanoparticles for effective drug delivery systems.

This study aimed to develop new organic/inorganic nanohybrids of targeted pullulan derivative/gold nanoparticles (FA-PABA-Q188-PUL@AuNPs) to improve the selectivity and efficacy of drugs. The chemical structure of targeted pullulan derivative, folic acid-decorated para-aminobenzoic acid-quat188-pullulan (FA-PABA-Q188-PUL), was designed for reducing, stabilizing, capping, and functionalizing AuNPs. Here, the key factors, including pH, temperature, and FA-PABA-Q188-PUL concentrations, were systematically optimized to control the morphology, size, and functionalization of multifunctional FA-PABA-Q188-PUL@AuNPs. Spherical FA-PABA-Q188-PUL@AuNPs obtained by a green, simple, and bio-inspired strategy under the optimum conditions were thoroughly characterized and had an average size of 12.6 ± 1.5 nm. The anticancer drug DOX was successfully loaded on monodispersed FA-PABA-Q188-PUL@AuNPs and the system exhibited excellent intracellular uptake, specificity, and physicochemical properties. The pH-responsive DOX release from FA-PABA-Q188-PUL@AuNPs-DOX showed fast release (85% after 72 h) under acidic conditions. Furthermore, FA-PABA-Q188-PUL@AuNPs-DOX enhanced the anticancer activity of DOX toward Chago-k1 cancer cells up to 4.8-fold and showed less cytotoxicity toward normal cells than free DOX. The FA-PABA-Q188-PUL@AuNPs-DOX induced the death of cells by increasing late apoptotic cells (26.4%) and arresting the cell cycle at S-G2/M phases. These results showed that innovative FA-PABA-Q188-PUL@AuNPs should be considered as new candidate platforms for anticancer drug delivery systems.

Quaternized chitosan-coated nanoemulsions: A novel platform for improving the stability, anti-inflammatory, anti-cancer and transdermal properties of Plai extract.

A new positively charged nanoemulsion using quaternized chitosan (QCS) as a protective layer was developed to improve the stability and bioactivity of lipophilic active components. The anti-inflammatory Plai extract was chosen as both an active ingredient and an oil phase of the system. Compared with chitosan-coated nanoemulsion (NE2-CS) and uncoated nanoemulsion (NE1), the QCS coating could improve the stability of the Plai extract during 28 days. The particle size of NE1 increased from 141 nm to 202 nm after coating with QCS, whereas zeta potential changed from -22.03 mV for NE1 to 20.23 mV for NE2-QCS, confirming the presence of QCS. A clear improvement in anti-inflammatory, anti-cancer, and transdermal properties of Plai extract was verified for NE2-QCS, which could be due to the NEs' fineness and the permanent positive charge of the protective layer. Therefore, we suggested that QCS-coated NEs can be used as an effective transdermal delivery system for lipophilic active components.

Facile and green synthesis of pullulan derivative-stabilized Au nanoparticles as drug carriers for enhancing anticancer activity.

In this work, we report for the first time AuNPs reduced/stabilized/capped with modified para-aminobenzoic acid-quat188-pullulan (PABA-QP) as excellent nanocarriers for delivery of doxorubicin to enhance the activity and safety of these systems. Spherical AuNPs@PABA-QP obtained by facile and green synthesis under optimum conditions were characterized by UV-VIS, TEM, EDS, SAED, XRD, ATR-FTIR and zeta-potential analyses and showed a narrow size distribution of 13.7 ±â€¯1.9 nm. DOX was successfully loaded onto AuNPs@PABA-QP via intermolecular interactions with high drug loading. DOX-AuNPs@PABA-QP (IC50 = 0.39µM) showed a 2.1-fold higher cytotoxicity against Chago cells than DOX alone (IC50 = 0.82µM), while exhibiting less cytotoxicity against normal cells (Wi-38). Moreover, DOX-AuNPs@PABA-QP also demonstrated high intracellular uptake by endocytosis, arrested in S and G2-M phases of the cell cycle (total S/G2-M increased to approximately 18.0%), induced excellent cytotoxicity, and increased the fraction of late-apoptotic cells (18.6%). Consequently, it is suggested that the novel combination of DOX-AuNPs@PABA-QP has the potential to be developed for human cancer treatment.

Synthesis and biological evaluation of novel 2-oxo-1,2-dihydroquinoline-4-carboxamide derivatives for the treatment of esophageal squamous cell carcinoma.

No new and effective treatments have been approved for the treatment of esophageal squamous cell carcinoma (ESCC) in the past decade. Cisplatin and 5-fluoruracil are the most commonly used drugs for this disease. In order to develop a new class of drugs effective in our ESCC phenotypic screens, we began a systematic approach to generate novel compounds based on the 2-oxo-1,2-dihydroquinoline-4-carboxamide fragment. Herein, we report on the synthesis and initial assessment of 55 new analogues in two ESCC cell lines. Some of the active analogues with IC50 values around 10 µM were tested in three additional cell lines. Our structure-activity relationships revealed remarkable alterations in the anti proliferative activities upon modest chemical modifications and autophagy modulation is a suggested mechanism of action.

Current Challenges and Opportunities in Treating Glioblastoma.

Glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, has a high mortality rate despite extensive efforts to develop new treatments. GBM exhibits both intra- and intertumor heterogeneity, lending to resistance and eventual tumor recurrence. Large-scale genomic and proteomic analysis of GBM tumors has uncovered potential drug targets. Effective and "druggable" targets must be validated to embark on a robust medicinal chemistry campaign culminating in the discovery of clinical candidates. Here, we review recent developments in GBM drug discovery and delivery. To identify GBM drug targets, we performed extensive bioinformatics analysis using data from The Cancer Genome Atlas project. We discovered 20 genes, BOC, CLEC4GP1, ELOVL6, EREG, ESR2, FDCSP, FURIN, FUT8-AS1, GZMB, IRX3, LITAF, NDEL1, NKX3-1, PODNL1, PTPRN, QSOX1, SEMA4F, TH, VEGFC, and C20orf166AS1 that are overexpressed in a subpopulation of GBM patients and correlate with poor survival outcomes. Importantly, nine of these genes exhibit higher expression in GBM versus low-grade glioma and may be involved in disease progression. In this review, we discuss these proteins in the context of GBM disease progression. We also conducted computational multi-parameter optimization to assess the blood-brain barrier (BBB) permeability of small molecules in clinical trials for GBM treatment. Drug delivery in the context of GBM is particularly challenging because the BBB hinders small molecule transport. Therefore, we discuss novel drug delivery methods, including nanoparticles and prodrugs. Given the aggressive nature of GBM and the complexity of targeting the central nervous system, effective treatment options are a major unmet medical need. Identification and validation of biomarkers and drug targets associated with GBM disease progression present an exciting opportunity to improve treatment of this devastating disease.

Novel organic/inorganic hybrid flower-like structure of selenium nanoparticles stabilized by pullulan derivatives.

We proudly present the first organic/inorganic hybrid pullulan/SeNPs hybrid microflower material obtained using a simple and bio-inspired strategy. The chemical structures of pullulan, folic acid decorated cationic pullulan (FA-CP) were designed for stabilizing selenium nanoparticles (SeNPs). SeNPs stabilized by FA-CP hybrid microflowers were observed after the addition of a cysteine hydrochloride solution into the solution mixture of Na2SeO3 and FA-CP. We suggested that the concentrations of cysteine and FA-CP were the key factors for the formation of flower-like structure. In addition, the formation mechanism of the microflowers was tentatively identified as anisotropic hierarchical growth. The microflowers exhibited effective drug adsorption with the loading capacity of 142.2 mg g-1 for doxorubicin which was three times higher than that for the doxorubicin-loaded spherical SeNPs and showed more potent activity against cancer cells while showing less toxicity against normal cells. These data demonstrated that the microflower-like FA-CP/SeNPs structure could be a candidate anticancer drug template in drug delivery systems.

pH-responsive selenium nanoparticles stabilized by folate-chitosan delivering doxorubicin for overcoming drug-resistant cancer cells.

Herein, we first report pH-responsive SeNPs stabilized with modified folic acid-N-trimethyl chitosan (TMC-FA) as nanocarriers for delivery of doxorubicin (DOX) to overcome drug-resistant cancer cells, which could enhance the activity of DOX by approximately 10-fold for a reduced IC50 value compared to free DOX. When nanoparticles were taken up by cells, the DOX-loaded SeNPs@TMC-FA demonstrated a faster release rate under acidic conditions. The cumulative release amount of DOX at pH 5.3 was 54.1% within 2h and 95.5% at 6h, whereas the release rate at pH 7.4 was 12.3% in 2h and 42.2% for 6h; release was not completed at the end of the study, 72h. Mechanistic studies suggested that DOX-SeNPs@TMC-FA induced cell death through the apoptosis pathway by involvement of caspase-3 and PARP proteins. The results demonstrated that pH-responsive SeNPs@TMC-FA, as targeted nanocarriers, promoted the efficacy of DOX and overcame drug resistance in NCI/ADR-RES cells.

Highly efficient and facile fabrication of monodispersed Au nanoparticles using pullulan and their application as anticancer drug carriers.

This work presented a simple, rapid, green and efficient approach to the synthesis of gold nanoparticles using pullulan as a reducing/stabilizing/capping agent for drug delivery systems to increase the safety and efficacy of these systems. Monodispersed AuNPs@pullulan with prolonged stability were fully characterized by UV-VIS, FTIR, TEM, EDX, TGA and zeta potential analyses. A mechanism of AuNPs formation was proposed in which pullulan created reducing species for the reduction of Au3+ to AuNPs (Au0) that resulted in the formation of spherical AuNPs@pullulan with an average size of approximately 11±5nm, while the hydroxyl groups of pullulan were oxidized to carboxylate compounds. Novel cassiarin A chloride derivatives (3d and 3i) as candidate anticancer drugs were successfully loaded onto AuNPs@pullulan through electrostatic interactions. AuNPs@pullulan-3d (IC50=6.0±0.1µM) and AuNPs@pullulan-3i (5.2±0.1µM) exhibited a 10.2-fold and 7.1-fold higher cytotoxicity against KATO-III cells than free compounds 3d (60.9±0.6µM), 3i (37.1±0.2µM) and cisplatin (64.5±0.9µM), respectively. AuNPs@pullulan exhibited high cellular uptake, biocompatibility and non-cytotoxicity to normal cells. Therefore, AuNPs@pullulan-3d or AuNPs@pullulan-3i have the potential to be developed for treatment of gastric cancer.

Tautomeric-Dependent Lactam Cycloaddition with Nitrile Oxide: Facile Synthesis of 1,2,4-Oxadiazole[4,5-a]indolone Derivatives.

A concise, metal-free, and gram-scale strategy to convert indoline-2,3-diones to 1,2,4-oxadiazole[4,5-a]indolones through an improved [3 + 2] cycloaddition of α-ketone-lactam with nitrile oxides has been developed. The lactim form of the resonance structure of isatin in protic solvents is the key active dipolarophile that shows chemo- and regioselectivity under experimental and theoretical conditions. This strategy conveniently enabled the assembly of several 1,2,4-oxadiazole[4,5-a]indolines with a broad range of functional groups. Compounds 3a and 4b exhibit cytotoxicity in the NCI/ADR-RES, SKOV3, and OVCAR8 cell lines.