Synergistic Agent Research Articles

Serum vitamin-D levels in relation to head and neck cancer

<br><b>Background</b><br>Vitamin D (VD) and its metabolites reduce the incidence of various cancers, including head and neck squamous-cell carcinoma (HNSCC) by inhibiting tumor angiogenesis, stimulating mutual adherence of cells, and enhancing intercellular communication, thereby strengthening the inhibition of cellular proliferation. Epidemiologic and case–control studies have demonstrated that low VD levels are associated with HNSCC risk. Some studies showed that patients with HNSCC who received VD at the time of diagnosis had diminished peripheral blood and intratumoral levels of immunosuppressive CD34 + cells and increased levels of mature dendritic cells. In addition, they showed the quantitative increase of the immune cells within the HNSCC tissue following VD treatment.<br><b>Aim</b><br>To investigate VD levels in head-cancer and neck-cancer patients as a step to further elucidate its association with head and neck cancer development, progression, and outcome.<br><b>Participants and methods</b><br>This study showed that VD deficiency is prominent in patients with head and neck cancer than in controls. Although it may increase patients' risk of therapy-related morbidity and poor outcome, it represents an inexpensive prophylactic and cost-effective option in the therapeutic armamentarium as a synergistic agent to traditional treatment strategies.<br><b>Results</b><br>The mean VD level in group A was 7.4 ± 2 ng/ml and for group B was 21 ± 6 ng/ml (<i>P</i>=0.043), indicating a significant decrease of VD in group A than in group B. Also, VD-deficiency status was significantly correlated with lower hemoglobin levels and with hepatitis C virus seropositivity in the studied cases.<br><b>Conclusion</b><br>This study showed that VD deficiency is prominent in patients with head and neck cancer than in controls. Although it may increase patients' risk of therapy-related morbidity and poor outcome, it represents an inexpensive prophylactic and cost-effective option in the therapeutic armamentarium as a synergistic agent to traditional treatment strategies.<br>

Influence of Zinc Oxide Nanoparticles and Char Forming Agent Polymer on Flame Retardancy of Intumescent Flame Retardant Coatings.

Zinc oxide nanoparticles (ZnO NPs) were synthesized by a precipitation method, and a new charring–foaming agent (CFA) N-ethanolamine triazine-piperazine, melamine polymer (ETPMP) was synthesized via nucleophilic substitution reaction by using cyanuric chloride, ethanolamine, piperazine, and melamine as precursor molecules. FTIR and energy-dispersive X-ray spectroscopy (EDS) studies were employed to characterize and confirm the synthesized ETPMP structure. New intumescent flame retardant epoxy coating compositions were prepared by adding ammonium polyphosphate (APP), ETPMP, and ZnO NPs into an epoxy resin. APP and ETPMP were fixed in a 2:1 w/w ratio and used as an intumescent flame-retardant (IFR) system. ZnO NPs were loaded as a synergistic agent in different amounts into the IFR coating system. The synergistic effects of ZnO NPs on IFR coatings were systematically evaluated by limited oxygen index (LOI) tests, vertical burning tests (UL-94 V), TGA, cone calorimeter tests, and SEM. The obtained results revealed that a small amount of ZnO NPs significantly increased the LOI values of the IFR coating and these coatings had a V-0 ratings in UL-94 V tests. From the TGA data, it is clear that the addition of ZnO NPs could change the thermal degradation behaviors of coatings with increasing char residue percentage at high temperatures. Cone calorimeter data reported that ZnO NPs could decrease the combustion parameters including peak heat release rates (PHRRs), and total heat release (THR) rates. The SEM results showed that ZnO NPs could enhance the strength and the compactness of the intumescent char, which restricted the flow of heat and oxygen.

Synthesis and Application of H-ZSM-5 Zeolites with Different Levels of Acidity as Synergistic Agents in Flame Retardant Polymeric Materials.

Several studies show a synergistic effect between intumescent formulations and aluminosilicates, such as zeolites and clays, but little is known about the effect of acidity of these additives on the synergistic action. In this work, H-ZSM-5 zeolite was submitted to desilication treatments for 30 min and for 2 h, and silicalite-1 was synthesized. The objective was to obtain samples of equivalent crystalline structure, but with different amounts of acid sites, in order to evaluate the effect of acid concentration of H-ZSM-5 zeolites on the synergistic action with an intumescent formulation composed by ammonium polyphosphate and pentaerythritol in polypropylene. H-ZSM-5 zeolites and silicalite were characterized by X-ray diffraction, nitrogen adsorption analysis and temperature-programmed desorption of ammonia. The desilication produced H-ZSM-5 zeolites with similar volumes of mesopores in both treatments, but the zeolite resulting from 2 h of desilication presented a higher concentration of acid sites than the zeolite from 30 min. The flame-retardant properties were evaluated by UL-94 classification, limiting oxygen index, glow-wire, thermogravimetric analysis and heating microscopy. The results showed that increasing the concentration and accessibility of the acid sites of H-ZSM-5 zeolites the flame-retardant properties of the studied composites improved. It is suggested that the increase of acid site concentration positively influences the catalysis of the reaction between ammonium polyphosphate and pentaerythritol, favoring the production of the precursors of the intumescent layer.

Programmable Ce6 Delivery via Cyclopamine Based Tumor Microenvironment Modulating Nano-System for Enhanced Photodynamic Therapy in Breast Cancer.

Photodynamic therapy (PDT) has shown great promise in breast cancer treatment. However, simplex target ligand modification or stimuli release cannot meet the requirement of effective drug delivery to solid tumor tissue. To overcome continuous bio-barriers existing in the tumor microenvironment, multi-stage response drug delivery was desirable. Herein, we developed a unique tumor microenvironment tailored nanoplatform for chlorin e6 (Ce6) delivery. We chose bovine serum albumin (BSA) as “mother ships” material for effective tumor periphery resident, cyclopamine (CYC) as extracellular matrix (ECM) inhibitor and synergistic anti-tumor agent, and diselenide containing amphiphilic hyaluronic acid-chlorin e6 polymers (HA-SeSe-Ce6) synthesized as “small bombs” for internal tissue destruction. The above three distinct function compositions were integrated into an independent CYC and HA-SeSe-Ce6 co-delivery albumin nano-system (ABN@HA-SeSe-Ce6/CYC). The obtained nano-system presents good biocompatible, long circulation and effective tumor accumulation. After entering tumor microenvironment, CYC gradually releases to disrupt the ECM barrier to open the way for further penetration of HA-SeSe-Ce6. Subsequently, targeted tumor cell internalization and intracellular redox response release of Ce6 would achieve. Moreover, CYC could also make up the deficiency of Ce6 in hypoxia area, owing to its anti-tumor effect. Improved therapeutic efficacy was verified in a breast cancer cell line and tumor-bearing mice model.

Ultrasound nanotheranostics in fighting cancer: Advances and prospects.

The intrinsic limits of conventional ultrasound microbubble contrast agent greatly promoted the development and application of various nanomaterials for more efficient cancer ultrasound theranostics. Considerable successes have been achieved in the field of ultrasound molecular imaging and targeted therapy for tumor based on nanoparticulate theranostic agents. This review summarizes and discusses the emerging development on exploring organic and inorganic nanomaterials for ultrasound-based tumor diagnositic applications, and as synergistic agents for ultrasound targeted therapy in fighting cancer. The relationship between structure/composition and functionality of nanomaterials for ultrasound theranostic is discussed and revealed in detail. Finally, the further development and challenges facing clinical implementation of ultrasound nanomedicine are discussed. As a highly promising and valuable tumor-specific theranostic methodology, it is believed that ultrasound nanomedicine would pave a novel but efficient way for combating cancer.

Preparation of hexakis (4‐aldehyde phenoxy) cyclotriphosphazene grafted kaolinite and its synergistic fire resistance in poly (butylene succinate)

AbstractHexakis (4‐aldehyde phenoxy) cyclotriphosphazene (HAPCP) was synthesized firstly and then it was grafted onto the exfoliated kaolinite (Kaol) to prepare K‐HAPCP. The structure of HAPCP and K‐HAPCP was well characterized. K‐HAPCP was used as synergistic agent in poly (butylene succinate) (PBS)/intumescent flame retardants (IFR) composites. The combustion behavior of PBS composites was reflected by limited oxygen index (LOI), vertical burning (UL‐94), and cone calorimeter test. The thermal stability was traced by thermogravimetric analysis. PBS is highly flammable with the LOI value of only 21.9% and cannot pass any UL‐94 grade during vertical burning test. By the presence of 22 wt% IFR and 3 wt% K‐HAPCP, the LOI of PBS composite is sharply increased to 40.3% and the sample can pass UL‐94 V‐0 rating with excellent anti‐dripping properties. Moreover, the degradation behavior is investigated and the probable flame retardant mechanism is also proposed.

Preliminary Report of MANIFEST, a Phase 2 Study of CPI-0610, a Bromodomain and Extraterminal Domain Inhibitor (BETi), in Combination with Ruxolitinib, in JAK Inhibitor (JAKi) Treatment Naïve Myelofibrosis Patients

Preliminary Report of MANIFEST, a Phase 2 Study of CPI-0610, a Bromodomain and Extraterminal Domain Inhibitor (BETi), in Combination with Ruxolitinib, in JAK Inhibitor (JAKi) Treatment Naïve Myelofibrosis Patients

Methyl-isobutyl ketone and 1-octanol as synergistic agents and phase modifiers in solvent extraction of cobalt(II) by the N-(2-hydroxybenzylidene)aniline from sulfate medium

The synergistic solvent extraction of cobalt(II) from sulfate medium with N-(2-hydroxybenzylidene) aniline in association of two synergistic agents, the methyl-isobutyl ketone (MIBK) and 1-octanolin chloroform at 25 °C, has been studied. Synergistic and antagonistic effects are observed for the title metal at low and high concentration ratios of the synergistic agents. The synergistic extraction of cobalt(II) with the mixtures has been investigated with the methods of slope analysis. The extracted species with the mixtures are CoL2(S)2 and CoL2 (HL) (S) (L, denoted N-(2-hydroxybenzylidene) aniline ion and S denoted MIBK or 1-octanol).

Synergistic effect of zeolite 4A on thermal, mechanical and flame retardant properties of intumescent flame retardant HDPE composites

The combination of synergistic agent with intumescent flame retardant (IFR) systems provides a promising way to prepare high performance IFR composites. In this study, the effects of the synthetic zeolite 4 A in combination with the IFR system consisting of ammonium polyphosphate (APP) and tris (2-hydroxyethyl) isocynurate (THEIC) on thermal degradation, mechanical properties, flame retardancy and char formation of high-density polyethylene composites were investigated by limiting oxygen index (LOI) measurement, cone calorimetry, scanning electron microscopy and laser Raman spectroscopy. The LOI value of HD/FR/Z-0.5 composite with an optimum content of 0.5 wt. % zeolite 4 A and 25 wt. % of total flame retardant reaches 26.3 %. A low loading of zeolite 4 A can improve the bench-scale combustion performance as determined by cone calorimetry, and promote the formation of more compact char residue with a highly graphitic structure. However, a low loading of zeolite in combination with the IFR system consisting of APP and THEIC produces no significant changes in mechanical performance.

Photo-degradation dynamics of five neonicotinoids: Bamboo vinegar as a synergistic agent for improved functional duration.

The effects of photo-degradation on the utilization of pesticides in agricultural production has been investigated. Various influencing factors were compared, with results showing that the initial pesticide concentration, light source, water quality and pH possessed different effects on neonicotinoids photo-degradation. The initial concentration and pH were found to be most critical effects. The photo-degradation rate decreased by a factor of 2-4 when the initial concentration increased from 5 mg L-1 to 20 mg L-1, particularly for acetamiprid and imidacloprid. The photo-degradation pathways and products of the five neonicotinoids were also investigated, with similar pathways found for each pesticide, except for acetamiprid. Degradation pathways mainly involved photo-oxidation processes, with products identified using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) found to be consistent with literature reported results. Bamboo vinegar exerted a photo-quenching effect on the neonicotinoids, with an improved efficiency at higher vinegar concentrations. The photo-quenching rates of thiamethoxam and dinotefuran were 381.58% and 310.62%, respectively, when a 30-fold dilution of vinegar was employed. The photo-degradation products in bamboo vinegar were identical to those observed in methanol, with acetic acid being the main factor influencing the observed quenching effects.

Calcineurin-Modulated Antimicrobial Peptide Expression Is Required for the Development of Helicoverpa armigera.

Helicoverpa armigera is a universal pest around the world that has been extensively used as a model organism for agricultural pests. Calcineurin (CAN) is an important Ca2+-dependent phosphatase that is participated in various biological pathways. Here, we revealed that CAN inhibition significantly arrested H. armigera larval development by reducing larvae weight, prolonging development time and reducing pupate rates. Furthermore, CAN serves as an immune activator and regulates antimicrobial peptide (AMP; cecropin D, attacin, and gloverin) expression by binding with relish transcript factor in H. armigera. This study provides a potential target to control H. armigera by using synergistic agents for pesticides or plant-mediated RNA interference technology.

Evaluation of Vitamin D3 level in sino-nasal polypi

Background: Vitamin D is a group of fat-soluble corticosteroid responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and multiple other biological effects. In humans, the most important compounds in this group are vitamin D3 [also known as cholecalciferol] and vitamin D2 [ergocalciferol].Aim of the work: The aim of this thesis is to assess Vitamin D3 [VD3] level in patients with sino-nasal polypi in comparison with normal individuals.Patients and Methods: This prospective comparative [case-control] study conducted by the Department of ENT, Al-Azhar University Hospitals in the period from March 2019 to September 2019 and included 40 individuals who were selected by inclusion and exclusion criteria, both genders, all patients had been counseled about the nature of the study and informed written consent has been obtained.Results: Serum level of VD3 in patients with chronic rhinosinusitis with sinonasal polyps [CRSwNP] and allergic fungal rhinosinusitis [AFRS] was significantly lower than that of control subjects. Vitamin D levels ranged from 8.74 to 39 ng/ml, and there was statistically significant decrease of serum vitamin D levels in patient group when compared to control group [16.20±4.29 vs 30.56±4.83 respectively]. In addition, there was significant increase of patients with deficient and insufficient vitamin D levels in patient group when compared to control group.Conclusion: VD3 may constitute an inexpensive prophylactic and cost effective option in the therapeutic armamentarium in reducing inflammation either by itself or as a synergistic agent to traditional agents in patients suffering from sino-nasal polypi.

1944P - Pharmacological screening with Chk1 inhibitors identifies synergistic agents to overcome resistance to platinums in basal breast and ovarian cancer

BackgroundMetastatic ovarian and basal-like breast cancers are incurable diseases with limited therapeutic options. In our study, we explored synergistic interactions of Chk1 inhibitors (rabusertib and SAR020106) with approved therapies in these indications. In addition, we evaluated the role of these agents to overcome platinum resistance. MethodsWe evaluate the effect of rabusertib and chemotherapic agents in ovarian (OVCAR3, OVCAR8, IGROV1, SKOV3) and breast (MDA-MB-231, HS578T, BT549, HCC3153) cancer cell lines. We also use the commercially available cell line A2780Rcis and a breast cancer model created in our laboratory, MDA-MB231Rcis. ResultsThe combination of platinum agents, cisplatin and carboplatin was synergistic with Chk1 inhibitors rabusertib and SAR020106 in most of basal-like and ovarian cancer cell lines. The combination of rabusertib with gemcitabine was very synergistic in basal-like cell lines but not in ovarian cancer. Doxorubicin, another DNA damaging agent, was also synergistic in ovarian cell lines, but showed less activity in the breast models. Combinations with topotecan were slightly synergistic only in basal-like tumors. The combination of rabusertib with agents that target mitosis were not synergistic. The combination of Chk1 inhibitor with platinum compounds or gemcitabine affects colony formation and tumor invasiveness. Combination of platinum agents and gemcitabine with rabusertib induced cell death that was mainly mediated by caspases. The effect of rabusertib on platinum resistance showed addition of Chk1 inhibitor to cisplatin induces cell death in cisplatin resistant cells. ConclusionsInhibition of Chk1 has a strong synergistic interaction with DNA damaging agents, including platinum compounds, gemcitabine and olaparib, on both tumor types. The effect of rabusertib with platinum agents and gemcitabine on colony growth and long-term effect confirms the effect on proliferation, invasion and long-term survival in basal-like and ovarian cancer cell lines. Addition of rabusertib to cisplatin induces cell death in all the cell lines including the resistant cells, demonstrate that resistance to cisplatin can be overcome by inhibition of Chk1 kinase. Legal entity responsible for the studyAlberto Ocaña. FundingInstituto de Salud Carlos III (PI16/01121) Diputación de Albacete and CIBERONC CRIS Cancer Foundation cancer association ACEPAIN research program of the UCLM regional fellowship for Biomedicine and Health science research (II-2018_11). DisclosureAll authors have declared no conflicts of interest.

Fast emerging insecticide resistance in Aedes albopictus in Guangzhou, China: Alarm to the dengue epidemic.

Dengue is one of the most serious mosquito-borne infectious diseases in the world. Aedes albopictus is the most invasive mosquito and one of the primary vectors of dengue. Vector control using insecticides is the only viable strategy to prevent dengue virus transmission. In Guangzhou, after the 2014 pandemic, massive insecticides have been implemented. Massive insecticide use may lead to the development of resistance, but few reports are available on the status of insecticide resistance in Guangzhou after 2014. In this study, Ae. albopictus were collected from four districts with varied dengue virus transmission intensity in Guangzhou from 2015 to 2017. Adult Ae. albopictus insecticide susceptibility to deltamethrin (0.03%), permethrin(0.25%), DDT(4%), malathion (0.8%) and bendiocarb (0.1%) was determined by the standard WHO tube test, and larval resistance bioassays were conducted using temephos, Bacillus thuringiensis israelensis (Bti), pyriproxyfen (PPF) and hexaflumuron. Mutations at the voltage-gated sodium channel (VGSC) gene and acetylcholinesterase (AChE) gene were analyzed. The effect of cytochrome P450s on the resistance of Ae. albopictus to deltamethrin was tested using the synergistic agent piperonyl butoxide (PBO). The results showed that Ae. albopictus populations have rapidly developed very high resistances to multiple commonly used insecticides at all study areas except malathion, Bti and hexaflumuron. We found 1534 codon mutations in the VGSC gene that were significantly correlated with the resistance to pyrethroids and DDT, and 11 synonymous mutations were also found in the gene. The resistance to deltamethrin can be significantly reduced by PBO but may generated cross-resistance to PPF. Fast emerging resistance in Ae. albopictus may affect mosquito management and threaten the prevention and control of dengue, similar to the resistance in Anopheles mosquitoes has prevented the elimination of malaria and call for timely and guided insecticide management.

Synergistic Antimicrobial Capability of Magnetically Oriented Graphene Oxide Conjugated with Gold Nanoclusters

AbstractBacterial resistance toward antibiotics has been a worldwide threat; one way to fight against the resistance is to develop a multimechanism antibacterial agent to achieve synergistic performance. Graphene oxide (GO) is an emerging antibacterial agent combining multiple mechanisms (physical insertion and chemical disruption), and its rich functional groups enable the complexation/conjugation of nanomaterials to further improve antibacterial performance. Herein, a synergistic antimicrobial agent is established through the assembly of paramagnetic holmium ions and gold nanoclusters (AuNCs) onto GO nanosheets. The assembled nanosheets can be vertically aligned under weak and practical magnetic fields (&lt;0.5 T ), providing high‐density sharp edges with preferential orientation to effectively pierce the bacterial membrane. Also, the conjugated AuNCs are efficiently delivered into bacteria to induce high oxidative stress, which strongly disturbs bacterial metabolism, leading to the death of both Gram‐positive and Gram‐negative bacteria. The antibacterial agent uses both physical (via oriented GO) and chemical (via GO and AuNCs) mechanisms to achieve synergistic antimicrobial performance with low IC50 values of 9.8 µg mL−1 on the basis of GO and 0.39 × 10−6 m on the basis of AuNCs. This multicomponent agent with dual antimicrobial mechanisms is expected to be a promising multifunctional‐antimicrobial agent with high biosafety.

Detoxification enzymes associated with butene-fipronil resistance in Epacromius coerulipes.

Epacromius coerulipes is a widely distributed locust pest species. Chemical control is the main method used to kill locusts; however, this can result in the selection of locusts with resistance to chemical pesticides. Therefore, the study of resistance is of great significance for the sustainable management of locusts. In this study, to investigate the relationship between detoxification enzymes and butene-fipronil resistance in E. coerulipes, resistant strains of the locust were compared with sensitive strains. The synergism of synergistic agents was significantly enhanced, and the activities of multifunctional oxidase, carboxylesterase, and glutathione sulfur transferase were significantly increased. Transcriptome sequencing revealed 226 detoxification enzyme genes and 23 upregulated genes. Neighbor-joining was used to construct a phylogenetic tree of related gene families, which included 59 P450 genes, 52 carboxylesterases (CarE) genes, and 25 glutathione S-transferase (GST) genes. Reverse transcription polymerase chain reaction (RT-PCR) analysis results of overexpressed genes in the resistant population combined with a phylogenetic tree showed that four P450 genes belonged to the CYP6, CYP4, CYP18 and CYP302 families, two CarE genes belonged to Clade A families, and one GST gene belonged to the Sigma family. These family members were annotated as detoxification enzyme genes of metabolic insecticide in the transcriptome databases. This study showed that P450, CarE and GST together resulted in moderate resistance to butene-fipronil in locusts. The analysis revealed several overexpressed detoxification enzyme genes that will be the focus of future studies on the mechanism of resistance to butene-fipronil. © 2019 Society of Chemical Industry.

Nanoemulsion Structural Design in Co-Encapsulation of Hybrid Multifunctional Agents: Influence of the Smart PLGA Polymers on the Nanosystem-Enhanced Delivery and Electro-Photodynamic Treatment.

In the present study, we examined properties of poly(lactide-co-glycolide) (PLGA)-based nanocarriers (NCs) with various functional or “smart” properties, i.e., coated with PLGA, polyethylene glycolated PLGA (PEG-PLGA), or folic acid-functionalized PLGA (FA-PLGA). NCs were obtained by double emulsion (water-in-oil-in-water) evaporation process, which is one of the most suitable approaches in nanoemulsion structural design. Nanoemulsion surface engineering allowed us to co-encapsulate a hydrophobic porphyrin photosensitizing dye—verteporfin (VP) in combination with low-dose cisplatin (CisPt)—a hydrophilic cytostatic drug. The composition was tested as a multifunctional and synergistic hybrid agent for bioimaging and anticancer treatment assisted by electroporation on human ovarian cancer SKOV-3 and control hamster ovarian fibroblastoid CHO-K1 cell lines. The diameter of PLGA NCs with different coatings was on average 200 nm, as shown by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. We analyzed the effect of the nanocarrier charge and the polymeric shield variation on the colloidal stability using microelectrophoretic and turbidimetric methods. The cellular internalization and anticancer activity following the electro-photodynamic treatment (EP-PDT) were assessed with confocal microscopy and flow cytometry. Our data show that functionalized PLGA NCs are biocompatible and enable efficient delivery of the hybrid cargo to cancer cells, followed by enhanced killing of cells when supported by EP-PDT.

Synergistic effect between solid wastes and intumescent flame retardant on flammability and smoke suppression of thermoplastic polyurethane composites

Phosphorus tailings and fly ash both are solid wastes and do harm to the environment. Here, they were added into thermoplastic polyurethane (TPU) matrices together with intumescent flame retardants (IFR), and the synergistic effects between IFR and phosphorus tailings or fly ash for improving the flame retardancy of TPU were investigated. The cone calorimeter test (CCT) results indicated that adding phosphorus tailings or fly ash substitute for part of IFR could obtain a better flame retardant effect. The peak heart release rate (PHRR) of TPU/25 wt% IFR composites exhibited a reduction of 77% than that of neat TPU, and the total smoke production presented a reduction of 16%. However, the PHRR value and total smoke production of the sample TPU/20 wt% IFR/5 wt% phosphorus tailings were reduced by 91% and 57%, respectively, compared to that of neat TPU. The dense char promoted by the presence of IFR and phosphorus tailings or fly ash delayed the diffusion of volatile pyrolysis products and transmission of heat and oxygen to the underlying material. Therefore, a certain amount of phosphorus tailings or fly ash can be used as synergistic agents with IFR to enhance the fire safety of TPU materials. From another aspect, it also provides a promising way for recycling use of phosphorus tailings and fly ash.

Melanin-dot-mediated delivery of metallacycle for NIR-II/photoacoustic dual-modal imaging-guided chemo-photothermal synergistic therapy.

Discrete Pt(II) metallacycles have potential applications in biomedicine. Herein, we engineered a dual-modal imaging and chemo-photothermal therapeutic nano-agent 1 that incorporates discrete Pt(II) metallacycle 2 and fluorescent dye 3 (emission wavelength in the second near-infrared channel [NIR-II]) into multifunctional melanin dots with photoacoustic signal and photothermal features. Nano-agent 1 has a good solubility, biocompatibility, and stability in vivo. Both photoacoustic imaging and NIR-II imaging in vivo confirmed that 1 can effectively accumulate at tumor sites with good signal-to-background ratio and favorable distribution. Guided by precise dual-modal imaging, nano-agent 1 exhibits a superior antitumor performance and less severe side effects compared with a single treatment because of the high efficiency of the chemo-photothermal synergistic therapy. This study shows that nano-agent 1 provides a promising multifunctional theranostic platform for potential applications in biomedicine.

Glycoalkaloids: Structure, Properties, and Interactions with Model Membrane Systems

The glycoalkaloids which are secondary metabolites from plants have proven to be of significant interest for their biological properties both in terms of their roles in plant biology and the effects they exhibit when ingested by humans. The main feature of the action of glycoalkaloids is their strong binding to 3β-hydroxysterols, such as cholesterol, to form complexes with the consequence that membrane structure is significantly perturbed, and leakage or release of contents inside cells or liposomes becomes possible. The glycoalkaloids have been studied for their ability to inhibit the growth of cancer cells and in other roles such as vaccine adjuvants and as synergistic agents when combined with other therapeutics. The glycoalkaloids have rich and complex physical behavior when interacting with model membranes for which many aspects are yet to be understood. This review introduces the general properties of glycoalkaloids and aspects of their behavior, and then summarizes their effects against model membrane systems. While there are many glycoalkaloids that have been identified, most physical or biological studies have focused on the readily available ones from tomatoes (α-tomatine), potatoes (α-chaconine and α-solanine), and eggplant (α-solamargine and α-solasonine).