Abstract

Graphical abstract

Keywords

Abbreviations

1. Introduction

2. Materials and methods

3. Results

4. Discussion

5. Conclusions

Author contributions

Declaration of Competing Interest

Acknowledgments

Appendix A. Supplementary data

References

Abstract

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

1. Introduction

As the third leading cause of cancer-related deaths worldwide (e.g., 881,000 deaths estimated in 2018)1, colorectal cancer (CRC, a cancer of the colon or rectum) is an obvious disease burden requiring effective, safe and widely-applicable treatments. Recent research in cancer immunology has led to the development of different immunotherapeutic strategies2, 3, 4. Among these, strategies that exert the blockade of immune checkpoint pathways [e.g., cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-L1)] have achieved favorable outcomes in a range of solid tumors5. However, it has been reported that only a minority of patients (up to 15% of the CRC population), who are identified with mismatch repair (MMR)-deficient CRC, respond positively to immune checkpoint blockade therapy6, while the response rate remains low in MMR-proficient CRC patients7. This failure is strongly attributed to the immunosuppressive feature of the tumor microenvironment (TME)8. Therefore, approaches designed to reprogram the TME may improve the therapeutic efficacy of immune checkpoint inhibitors9, potentially providing therapeutic benefit for the wide spectrum of CRC patients.

Immunogenic cell death (ICD) is characterized as immunogenic apoptosis that activates damage-associated molecular patterns (DAMPs) in dying or dead tumor cells in response to certain stimuli10. DAMPs as danger signals activate dendritic cells (DCs) for the presentation of tumor-associated antigens (TAAs), which subsequently induce T cell-mediated immunological responses against living tumor cells of the same kind10. The concept of ICD has revolutionized the traditional view of chemotherapeutic agents that are considered cytotoxic and poorly immunogenic. For example, chemotherapeutic drugs such as anthracyclines11, oxaliplatin12, bortezomib13 and cardiac glycosides14 have been identified as the putative ICD inducers. Recently, evaluation of chemotherapeutics as potential ICD inducers has gained increasing attention. In addition, ICD is often concomitant with the production of reactive oxygen species (ROS)10, and the efficacy of ICD may be enhanced by ROS-inducing strategies15, 16, 17. Therefore, it is hypothesized that a combination of ICD- and ROS-inducing strategies will mediate the remodeling of immunosuppressive TME and achieve synergistic immunotherapeutic efficacy with immune checkpoint blockade.

Abstract

Keywords

1. Introduction

2. DNA damage response

3. DDR and radiotherapy failure

4. DDR inhibitors decrease radio-resistance

5. DDR roles in chemotherapy failure

6. DDR inhibitors decrease chemo-resistance

7. Conclusions

Funding

Availability of data and material

Ethics approval and consent to participate

Consent for publication

Declaration of Competing Interest

Acknowledgements

References

Abstract

Up to now, many improvements have been made in providing more therapeutic strategies for cancer patients. The lack of susceptibility to common therapies like chemo- and radio-therapy is one of the reasons why we need more methods in the field of cancer therapy. DNA damage response (DDR) is a set of mechanisms which identifies DNA lesions and triggers the repair process for restoring DNA after causing an arrest in the cell cycle. The ability of DDR in maintaining the genome stability and integrity can be favorable to cancerous cells which are exposed to radiation therapy or are treated with chemotherapeutic agents. When DDR mechanisms are error-free in cancer cells, they can escape the expected cellular death and display resistance to treatment. In this regard, targeting different components of DDR can help to increase the susceptibility of advanced tumors to chemo- and radio-therapy.

1. Introduction

DNA-damaging agents originating whether from endogenous or exogenous resources are known to threat the viability of every cell of our body [1]. Besides to the cellular issues arising from the great number of mutations and genome instability, the lack of proper responses can establish generations of these defective cells and put our whole body in danger [1]. DNA damage response or DDR is a precise mechanism which contains sensing the lesions, establishing signals, and finally initiating repair processes by the means of these signals [2]. During DDR, cell cycle is also affected by the mediators of DDR and is temporarily stopped in order to inhibit the replication of a defective DNA [3]. In some cases, DNA deteriorations are irreparable and thus, cell death is the only option on the table [3].

In addition to normal cells, cancerous cells are also able to use the same mechanisms for their chemotherapy- and/or radiotherapy-induced damaged DNA. Until DDR is working properly in a cancerous cell, DNA damages would not lead to cell death and thus, treatment would not be considered successful [1]. This means that despite all the advantageous impacts of DDR, it stands in the way of overcoming a great challenge in cancer therapy: resistance to our common methods, chemo- and radio-therapy. Recently, a great number of researchers have worked on targeting distinct components of DDR for enhancing the efficacy of cytotoxic treatments [4]. In this paper, we review the process of DDR briefly and explain the role of its key players in decreasing the susceptibility of cancer cells to common therapeutic procedures. Additionally, the usage of DDR inhibitors on different types of cancer would be discussed for giving an insight for the treatment of advanced stages of this lethal disease.

1- Introduction

2- Experimental section

3- Results and discussion

4- Conclusions

References

Abstract

In this paper, a targeting hyaluronic acid (HA)/mesoporous silica nanoparticle (MSN) based drug delivery system (DDS) with dual-responsiveness was prepared for cancer therapy. To avoid the side reaction between the anti-cancer drug doxorubicin hydrochloride (DOX) and HA, host-guest interaction was applied to fabricate the DDS named DOX@MSN-SS-N=C-HA. The “nanocontainer” MSN was modified with benzene ring via both pH-sensitive benzoic imine bond and redox-sensitive disulfide linkage. When DOX was loaded in the pores of MSN, the channels were then capped by the “gatekeeper” β-CD grafted HA (HA-g-CD) through host-guest interaction between β-CD and benzene. HA endowed the drug carriers with the targeting capability in CD44 over-expressed cancer cells. After cellular uptake, the carriers could rapidly release DOX for cell apoptosis due to both the hydrolysis of benzoic imine bond at low pH and the cleavage of disulfide bond at a high concentration of glutathione (GSH) intracellular. In vitro drug release studies and in vitro cytotoxicity studies were taken to investigate the dual-responsiveness of the carriers. And the CD44-receptor mediated cancer cell targeting capability was investigated as well. In conclusion, the targeted dual-responsive complex DDS fabricated through host-guest interaction has promising potential in cancer therapy.

Introduction

Chemotherapy remains one of the major therapeutic approaches applied to treat cancer in clinic. However, the disadvantages of traditional chemotherapeutic drugs such as unfavorable pharmacokinetics, poor biodistribution and lack of selectivity for target tissues reduce the utilization of the drugs and cause serious side effects [1]. To tackle these problems, anti-cancer drug delivery systems (DDSs) based on nanotechnology have been introduced and developed rapidly in recent decades [1–4]. DDSs such as liposomal daunorubicin (DaunoXome), pegylated liposomal doxorubicin (Doxil), albumin nanoparticle based Nan-paclitaxel (Abraxane) and polymeric micelle paclitaxel (GenexolPM) have already been approved for clinical treatment of cancer [3,4]. These nanosized DDSs can be accumulated in tumor tissues more easily via enhanced permeability and retention (EPR) effect to improve the pharmacokinetics and biodistribution of the drugs, as well as to reduce their side effects [5]. Though the commercial DDSs represented by the liposomal doxorubicin can overcome part of the shortcomings of traditional anticancer drugs, they cannot or only modestly improve patients’ overall survival [3,6–9]. Therefore, more efforts are needed to develop novel advanced DDSs. The properties including controlled drug release based on stimuli- sensitivity [10,11] and ligand-mediated active cancer targeting [12–15] introduced make the newly reported DDSs with better therapeutic effects [1–4]. During the past decade, mesoporous silica nanoparticle (MSN) based DDSs have attracted considerable attention from scientists worldwide [16,17]. MSNs can be simply synthesized with tunable size, shape, pore size and volume [17,18], and are easy surface functionalization [16]. These advantages, as well as the high drug loading capacity and good biocompatibility, ensure that MSNs are excellent choices for designing safe and efficient drug carriers [16–18].

1- Introduction

2- Material and methods

3- Results and discussion

4- Conclusions

References

Abstract

Mesoporous silica nanoparticles with folic acid (MSN−COOH-Tet-HBP-FA) are able to mediate targeting and have a pH stimulation response character, and therefore have been successfully synthesized as vectors for antitumor drug delivery. The model drug is tetrandrine (Tet). The chemical structure and properties of these NPs were characterized through systematic characterization analyses. Their drug loading capacity was significantly improved through carboxy modification (26.86 % in max), and they exhibited pH-dependent drug release profiles(“zero pre-release” within 20 h in a normal physiological environment). In vitro cytotoxicity and cell uptake of the as-synthesized NPs in Hela and A549 cells were also evaluated, and exhibited high cytotoxicity and cell-targeted uptake capacity. It was concluded that MSN−COOH-Tet-HBP-FA could be used as a promising drug delivery system for cancer therapy.

Introduction

Cancer is currently considered to be a leading factor that threatens human lives, and chemotherapy remains one of the most common methods used for cancer treatment. However, traditional drugs are nonspecific and cannot discriminate cancer cells and normal cells, which not only limits the accumulation of drugs in tumor cells, but also leads to systemic toxicity and adverse side effects. In order to improve the efficacy of chemotherapy, many studies have been devoted to the development of tumor-targeted nanocarriers, which can be used to control the delivery of antitumor drugs. Using the enhanced permeation and retention (EPR) effects, researchers have developed multiple nanocarrier platforms, including liposomes, polymer nanoparticles, nano-micelles, and dendrimers, which are used to delivery anticancer drugs into tumor tissues. However, the EPR effect is not efficient enough to eradicate the side effects of cytotoxic drugs and to exert the anticancer therapy selectively in cancer cells. In order to enhance the targeting and tumoral uptake ability, the external surface of nanocarrier is often modified with various ligands, which can significantly enhance the interaction between the cancer cells and the nanocarriers[. Targeted agents typically include antibodies (such as monoclonal antibodies), peptides (such as Arg-Gly-Asp (RGD)), and small molecule compounds (such as folic acid).

1- Introduction

2- Materials and methods

3- Results and discussion

4- Conclusions

References

Abstract

Nowadays, a combinatorial drug delivery system that simultaneously transports two or more drugs to the targeted site in a human body, also recognized as a dual-drugs delivery system, represents a promising strategy to overcome drug resistance. Solid lipid nanoparticles loaded with clotrimazole (CLZ) and alphalipolic acid (ALA), considered as an effective agent in the reduction of reactive oxygen species, can enhance anti-infective immunity being proposed as a non-toxic and mainly non-allergic dual-drugs delivery system. In this study, uncoated and cationic CLZ-ALA-loaded SLN were prepared and compared. Suspensions with a narrow size distribution of particles of mean size below 150 nm were obtained, having slight negative or highly positive zeta potential values, due to the presence of the cationic lipid, which also increased nanoparticles stability, as confirmed by Turbiscan® results. Calorimetric studies confirmed the rationale of separately delivering the two drugs in a dual-delivery system. Furthermore, they confirmed the formation of SLN, without significant variation in presence of the cationic lipid. In vitro release studies showed a prolonged drug release without the occurrence of any burst effect. In vitro studies performed on 25 strains of Candida albicans showed the antimicrobial drug activity was not altered when it was loaded into lipid nanoparticles. The study has proved the successfully encapsulation of CLZ and ALA in solid lipid nanoparticles that may represent a promising strategy to combine ALA protective effect in the treatment with CLZ.

Introduction

Fungal infections, most of all candidiasis, represent an increasing challenge affecting global health, that in many cases produces morbidity and mortality in immunocompromised and intensive care unit patients [1,2]. Among different types of fungi, Candida albicans represents the main cause of fungal diseases, responsible of both orally and vaginally yeast infections, overall when a decrease in Lactobacillus concentration appears [3]. Usually, polyenes, echinocandins and azoles are the most used drugs for the treatment of fungal infections [4], even if the requirement of early treatment and the occurrence of side effects still limit the efficiency of the therapy. Among azoles, Clotrimazole (CLZ) is one of the most broad-spectrum antimycotic drug used for the treatment of vulvovaginal and oropharyngeal candidiasis [5]. Moreover, CLZ has been claimed to show a selective antibacterial activity [6,7] and ability to inhibit in vitro Streptococcus mutans biofilm and virulence [8]. CLZ antifungal activity is related to its capability to interfere with the biosynthesis of ergosterol, the major component of the fungal cytoplasmic membrane, with the consequent depletion of ergosterol and its replacement with the aberrant sterol species, 14-amethylsterol, thus disturbing the membrane permeability and fluidity [9]. However, the increasing antifungal resistance to azoles, mainly among immunocompromised patients, strongly limits the effective treatment of mycoses [10]. Combinatorial drug delivery is a promising strategy to prevent potential drug resistance [11]. We have recently demonstrated the possibility to improve CLZ effectiveness exploiting its nanoencapsulation in lipid nanoparticles prepared by additionally using of essential oils from Mediterranean area, highlighting their synergistic effect [12].

1- Introduction

2- Materials and methods

3- Results and discussion

4- Conclusions

References

Abstract

Traditional wastewater treatment plants cannot completely remove trace pharmaceutical and personal care products. In particular, quinolone antibiotics are mainly adsorbed on microbial cell surfaces in excess sludge and are released into the water environment during agricultural supplementation, mainly due to the exfoliation of extracellular polymeric substances (EPS) caused by changes in environmental conditions. Here, the occurrence of seven typical quinolone antibiotics from three generations in excess sludge was investigated at trace concentrations using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). EPS facilitated adsorption independent of pH and quinolone antibiotic type, and the solid-liquid distribution coefficient decreased markedly as pH increased (pH 5–9, range of municipal wastewater). Metal ions bound in EPS were predominantly responsible for the adsorption of antibiotics in sludge, rather than the macroscopic size of the sludge floc. pH affected patterns of quinolone antibiotics, the zeta potential of sludge floc, and the contents of metal ions contained in sludge. The adsorption capacity of antibiotics first increased and then decreased with increasing pH in the range of pH 3–11, reaching a maximum (20,506, 14,458, 10,689, 22,854, 20,302, 8494, and 29,547 L/kg for CIP, ENR, LOM, MOX, NOR, OFL, and SAR, respectively) near pH 5, at which the cationic bridging of Ca2+ and Mg2+ bound in EPS played a major role owing to their larger ion radius and higher contents in excess sludge. Due to high surface heterogeneity of sludge, the Freundlich model was more suitable than the Langmuir model for describing the adsorption behavior of quinolone antibiotics. These results provide further insight into the release of quinolone antibiotics adsorbed in excess sludge, with potential implications for the agricultural use of sludge.

Introduction

Trace pharmaceutical and personal care products (PPCPs) have been detected in environmental media such as surface water, groundwater, and soil. Although the concentration of PPCPs related to human activities is usually on the order of nanograms to micrograms per liter in the water environment [1–5], many PPCPs are discharged continuously into the environment, causing potential risks for human health and the environment due to their ongoing utilization [6–9]. Wastewater treatment plants (WWTPs) are one of the main point sources of PPCP discharge into the environment [10], as it is difficult to biochemically degrade these substances during the conventional wastewater treatment process [11]. As a result, except for a small amount of PPCPs that are released into the atmosphere by escape, some portion of PPCPs remains in the effluent of the wastewater treatment plant, with the remainder present in excess sludge due to adsorption or dissolution [12]. The Water Pollution Prevention Action Plan promulgated in April 2015 in China stipulates that treated sludge cannot contain potential environmental pollutants [13]. When excess sludge containing PPCPs is used for land use and agricultural production activities such as fertilization, PPCPs in the sludge may be released into the environment as the external environment changes [10,14–19], thereby contaminating surface water and groundwater [4,12,18–20]. In recent years, quinolone antibiotics have been one of the most widely used antibiotics in veterinary and medical applications [21]. In China, they are widely used in human clinical settings and livestock breeding for disease prevention, with livestock and poultry farming accounting for about 50% of their use [22]. Moreover, the consumption of quinolone antibiotics has increased significantly; for example, the annual consumption of quinolone antibiotics in humans and animals in 1998 was 1,350 and 470 tons respectively [23], while the annual consumption of ciprofloxacin, norfloxacin, ofloxacin, lomefloxacin, and enrofloxacin in China in 2013 for both humans and animals reached 5340, 5440, 5110, 1250, and 5180 tons, respectively [22].

1- Introduction

2- Experimental

3- Results and discussion

4- Conclusion

References

Abstract

In this work, the bulk and surface composition of Fe3O4 supermagnetic nanoparticles were modified for efficient epoxy curing. The bare, ethylenediaminetetraacetic acid (EDTA) capped, and cobalt (Co)-doped EDTA capped Fe3O4 nanoparticles were synthesized electrochemically. The crystalline structure and phase information, surface capping, morphology and magnetization behavior of nanoparticles were studied by X-Ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FE-SEM) and vibrating sample magnetometer (VSM), respectively. A low amount of the prepared nanoparticle (0.1 wt.%) was used in preparation of epoxy nanocomposites. Nonisothermal differential scanning calorimetry (DSC) under different heating rates was performed to study the potential of nanoparticles in curing epoxy resin with an aliphatic amine. The heat release data on nanocomposites suggest that EDTA capped Co-doped Fe3O4 considerably improved the curing reaction between epoxy resin and the curing agent. Calculations based on Cure Index approved qualitatively a shift from Poor to Good cure by concurrent lattice and surface modifications of magnetic nanoparticles. It is bielived that the approach used in this work can pave the way to enhance curability of epoxy nanocomposites by the combined modification of bulk and surface of nanoparticles.

Introduction

Addition of nanoparticles and their surface functionalization has been practised over the past three decades in order to enhance the ultimate properties and performance of organic coatings [1–5]. A Nevertheless, there is a need for looking at properties of coatings containing functionalized nanoparticles from a molecular perspective so as to be able to tune properties by controlling the curability of thermoset resins under the influence of surface-functionalized nanoparticles. The difficulty is that no molecular-level gauge is available for quantifying the status quo of cross-link density of thermoset nanocomposite to assess whether or not functionalized nanoparticles added to the system are reactive towards curing moieties [6–8]. The effect of surface modification of a wide variety of nanoparticles with low- and high-molecular weight molecules of amine, carboxylic and hydroxyl on the curability of epoxy resin was addressed in previous works of this group, which are including carbon nanotubes (CNTs) [9–11], graphene oxide (GO) nanoflakes [12–14], halloysite nanotubes (HNTs) [15–17], silica nanoparticles [18,19] and zinc oxide (ZnO) nanoparticles [20]. Reports suggest that surface functionalization of nanoparticles with high-molecular-weight ethylenediaminetetraacetic acid (EDTA) can affect ultimate properties of cross-linkable polymer nanocomposites. For instance, Syuhada et al. showed that EDTA surface-functionalized GO was dispersed well in chitosan matrix due to interaction of EDTA functional groups with chitosan [21]. Well-dispersed GO-EDTA in chitosan matrix led to facilitation of stress transfer resulting in 71% improvement in tensile strength compared to the neat chitosan film.

Abstract

The aims of this paper are: (1) to review the current state of the art in the field of cartilage substitution and regeneration; (2) to examine the patented biomaterials being used in preclinical and clinical stages; (3) to explore the potential of polymeric hydrogels for these applications and the reasons that hinder their clinical success. The studies about hydrogels used as potential biomaterials selected for this review are divided into the two major trends in tissue engineering: (1) the use of cell-free biomaterials; and (2) the use of cell seeded biomaterials. Preparation techniques and resulting hydrogel properties are also reviewed. More recent proposals, based on the combination of different polymers and the hybridization process to improve the properties of these materials, are also reviewed. The combination of elements such as scaffolds (cellular solids), matrices (hydrogel-based), growth factors and mechanical stimuli is needed to optimize properties of the required materials in order to facilitate tissue formation, cartilage regeneration and final clinical application. Polymer combinations and hybrids are the most promising materials for this application. Hybrid scaffolds may maximize cell growth and local tissue integration by forming cartilage-like tissue with biomimetic features.

Introduction: Current Clinical Approaches and the Need for New Developments

The aim of this paper is to review the current state of the art of materials for cartilage substitution and regeneration. Section 1 describes the current state of the art in clinical treatments. Polymeric hydrogels used in cartilage regeneration and the reasons hindering their clinical success are reviewed in Section 2. The preparation techniques using polysaccharides and the resulting hydrogel properties are described in Section 3. Finally, future trends are explored in Section 4. Several reviews about hydrogels for cartilage regeneration have been published for the last 10 years, focusing on preparation and characterization, natural and synthetic polymer precursors, gelation kinetics, cell and drug delivery, growth factors, mechanical properties and biocompatibility. Nevertheless, most of those reviews do not propose new alternatives to improve hydrogels properties which can fulfill the real clinical needs in terms of tissue regeneration, mechanical properties and degradation kinetics. Therefore, this paper reviews relevant literature published during 2013–2017, related to the application, fabrication, characterization, in vitro and in vivo assays of biomaterials based on hydrogels for cartilage regeneration. The studies selected are articles and reviews written in English.

Abstract

Bismuth (Bi) and Nickel (Ni) Doped Titanium Dioxide (TiO2) nanoparticles were synthesized by sol–gel method and the prepared nanoparticles were characterized by X-Ray Diffraction, Scanning Electron Microscope, UV–vis reflectance spectroscopy and Brunauer–Emmett–Teller (BET) analysis. The concentration of dopant in synthesized catalysts was varied from 0.25 to 1.0 wt%. Maximum BET surface area of 47.8 and 45.7 m2/g was observed with 0.25 wt% Bi–TiO2 and 0.5 wt% Ni–TiO2, respectively. EDX analysis has established the presence of 0.21% Bi ions and 0.36% Ni ions in 0.25 wt% Bi doped TiO2 and 0.5 wt% Ni doped TiO2, respectively. Band gap of Bi–TiO2 (0.25 wt%) and Ni–TiO2 (0.5 wt%) was obtained to be 2.99 eV, which is found to be minimum among the various synthesized catalysts. The photocatalytic activity of synthesized catalysts were tested and compared with Degussa TiO2 for degradation of Ibuprofen (IBP) as a model compound. Bi–TiO2 nanoparticles revealed higher photocatalytic activity when compared to Ni–TiO2 or Degussa TiO2 under solar irradiation, which may be attributed to increase in specific surface area, and decrease in the crystallite size. Maximum of 89% degradation was achieved with 0.25% Bi–TiO2 photocatalyst under 6 h of illuminations with a solar light, whereas, 78% degradation has been achieved under similar experimental condition with Ni doped TiO2. The kinetics of the degradation of IBP has been explained in terms of the Langmuir–Hinshelwood model and was found to follow first order kinetics with k value of 0.0064 and 0.0046 min−1 with Bi and Ni doped TiO2, respectively.

Introduction

The existence of pharmaceuticals compounds and its residues has been reported frequently in literature (Melo et al. 2009; Halling-Sorensen et al. 1998) thus, receiving increasing attention as an emerging environmental issue. Numerous pharmaceutical compounds have been noticed in household wastewater, natural water bodies and groundwater in many countries all over the world. The Presence of pharmaceutical compounds can cause severe environmental issues due to the chemical toxicity of the lively constituents in the formulations and sometimes, of their disintegration products. Ibuprofen [IBP] is one of the most commonly consumed medicines worldwide, mainly due to its use as a pain reliever. Concentration of IBP in the environment has been stated between 10ng/L to 169µg/L (Santos et al. 2007). Sources of these contaminants are primarily the domestic waste water due to excretion of non-metabolized drugs by animal or human urine and feces. Conventional treatment processes functional at sewage treatment plants are not efficient in removing such pharmaceutical substances by various physical or biological treatment steps. Therefore, alternative and effective treatment methods need to be explored for the degradation of such pharmaceutical compounds.

Abstract

Graft copolymerization of diallyldimethylammonium chloride (DADMAC) vinyl monomer together with N,N‘- methylene-bis-acrylamide (MBA) crosslinking agent onto water soluble carboxymethyl cellulose CMC was carried out using ammonium persulfate (APS) initiator . The copolymerization resulted in hydrogels. Characterization and properties of these hydrogels were dependent on conditions affecting the copolymerization reaction and, in turn, control the pore size and porous structure of the hydrogels. Thus increasing the monomer concentration causes outstanding enhancement in the swelling ratio of the hydrogel provided that monomer is used at a concentration of 40% or more .The opposite holds true for initiator concentration; the swelling ratio of the hydrogel decreases significantly by increasing APS concentration from 0.05 to 0.25 mole/L. With respect to MBA crosslinker, maximum swelling ratio of 30 could be achieved with hydrogel prepared using MBA at concentration of 0.1 mole/L; hydrogel prepared in presence of MBA at 0.05 mole/L exhibits zero swelling ratio while hydrogel prepared using MBA at 0.3 mole/L displays swelling ratio of 10%, maximum swelling ratio for hydrogel could achieved at pH7 .Striking decrease in the swelling ratio of hydrogel is observed within pH range 2-6 as well as at pH 8. The hydrogel could also be successfully attached to modified cotton fabric, namely partially carboxymethylated cotton (PCMC) through ionic crosslinking The in situ formation of CuO nanoparticles inside the matrix of CMC-DADMAC hydrogel nanocomposites attached to cotton fabric was also investigated .The formation of CuO nanoparticles in the hydrogels was confirmed using X-ray diffraction and scanning electron microscopy studies. Furthermore, the functional performance of the novel CuO nanocomposite hydrogel as wound dressing was tested for antibacterial activities; the nanocomposite hydrogels demonstrated excellent antibacterial effect. The work was further extended to include synthesis and Page 1 of 28 RSC Advances 2 characterization of Ag/CMC-DADMAC hydrogel nanocomposites. The latter displays high antibacterial activity.

Abstract

At the atomic-cluster scale, pure boron is markedly similar to carbon, forming simple planar molecules and cage-like fullerenes. Theoretical studies predict that two-dimensional (2D) boron sheets will adopt an atomic configuration similar to that of boron atomic clusters. We synthesized atomically thin, crystalline 2D boron sheets (i.e., borophene) on silver surfaces under ultrahigh-vacuum conditions. Atomic-scale characterization, supported by theoretical calculations, revealed structures reminiscent of fused boron clusters with multiple scales of anisotropic, out-of-plane buckling. Unlike bulk boron allotropes, borophene shows metallic characteristics that are consistent with predictions of a highly anisotropic, 2D metal.

Bonding between boron atoms is more complex than in carbon; for example, both two- and three-center B-B bonds can form (1). The interaction between these bonding configurations results in as many as 16 bulk allotropes of boron (1–3), composed of icosahedral B12 units, small interstitial clusters, and fused supericosahedra. In contrast, small (n < 15) boron clusters form simple covalent, quasiplanar molecules with carbon-like aromatic or anti-aromatic electronic structure (4–7). Recently, Zhai et al. have shown that B40 clusters form a cage-like fullerene (6), further extending the parallels between boron and carbon cluster chemistry.

To date, experimental investigations of nanostructured boron allotropes are notably sparse, partly owing to the costly and toxic precursors (e.g., diborane) typically used. However, numerous theoretical studies have examined two-dimensional (2D) boron sheets [i.e., borophene (7)]. Although these studies propose various structures, we refer to the general class of 2D boron sheets as borophene. Based upon the quasiplanar B7 cluster (Fig. 1A), Boustani proposed an Aufbau principle (8) to construct nanostructures, including puckered monolayer sheets (analogous to the relation between graphene and the aromatic ring). The stability of these sheets is enhanced by vacancy superstructures (7, 9) or out-of-plane distortions (10, 11). Typically, borophene is predicted to be metallic (7, 9–12) or semimetallic (10) and is expected to exhibit weak binding (13) and anisotropic growth (14) when adsorbed on noble-metal substrates. Early reports of multiwall boron nanotubes suggested a layered structure (15), but their atomic-scale structure remains unresolved. It is therefore unknown whether borophene is experimentally stable and whether the borophene structure would reflect the simplicity of planar boron clusters or the complexity of bulk boron phases.

Introduction

The major aim of developing nanocarrier drug delivery systems is to enhance the therapeutic effect or reduce toxicity of therapeutically active materials. This is conventionally achieved using spherically shaped vesicle nanocarriers such as liposomes. Alternatively, carbon nanotubes (CNTs) are essentially cylindrical molecules made of carbon atoms. CNTs are graphene sheets rolled into a seamless cylinder that can be open ended or capped, having a high aspect ratio with diameters as small as 1 nm and a length of several micrometers. CNTs made from a single graphene sheet results in a single-walled nanotubes (SWNT) while several graphene sheets make up multiwalled carbon nanotubes (MWNTs) [1, 2] (Figure 1). Ever since their discovery in 1991 by Iijima [1], there has been intense interest in these allotropes of carbon due to their unique physical and chemical properties and potential applications in a wide range of fields, from electronic devices and sensors to nanocomposite materials of high strength and low weight. Pristine CNTs are not soluble. It was only after the development of strategies to functionalize these molecules with organic groups and render them soluble that opened the way to bioapplications of CNTs. Due to their high surface area, they are capable of adsorbing or conjugating with a wide variety of therapeutic molecules. Thus, CNTs can be surface engineered (i.e., functionalized) in order to enhance their dispersability in the aqueous phase or to provide the appropriate functional groups that can bind to the desired therapeutic material or the target tissue to elicit a therapeutic effect. CNTs might help the attached therapeutic molecule to penetrate through the target cell to treat diseases [3–6] and a recent example of CNTs with a variety of functional groups relevant to cancer therapy [7] is shown in Figure 2. Here, we provide an overview of the therapeutic applications of CNTs with a major focus on their use in the treatment of cancer.

INTRODUCTION

Codeine is one of the main alkaloids in poppy seed having pharmacological and toxicological activity (Fig. 1). As a drug, codeine is widely used as a good analgesic and cough suppressant agent [1,2]. It is a derivative of morphine, one of the best known drug abuses. Excessive or habitual use of these drugs causes toxic symptoms. Additionally, it has been reported that addiction to poppy drug abuse leads to a lot of sever social problems [3]. Thus, the rapid separation and determination of small level of codeine in biological fluid is of vital interest in clinical toxicology, control of drug abuse and forensic cases.

A wide rang of analytical methods have been reported for the determination of codeine such as gas chromatography [4,5], high performance liquid chromatography [6,7] and ion selective electrode [8]. Sample preparation techniques prior to instrumental analysis were based on liquid-liquid extraction (LLE) [9] and solid phase extraction (SPE) [10-13]. Unfortunately, these methods require a large sample volume and are time consuming. In particular, the traditional liquidliquid extraction method used large amounts of hazardous, volatile organic solvents. So, in recent years, the green liquidliquid extraction and cloud point extraction (CPE) have been employed in analytical chemistry. The use of preconcentration step based on phase separation by cloud point technique offers a convenient alternative to more conventional extraction system. Compared with the traditional organic liquid-liquid extraction, cloud point extraction requires a very small amount of relatively nonflammable and nonvolatile surfactants that are friendly to the environment. The first applications of phase separation based on cloud point phenomenon refer to the extraction of metal ions forming complexes sparingly soluble in water. Another application focuses on the isolation and purification of species of biological interest, mainly proteins [14]. This methodology was used first by Bordier [15] for the separation of hydrophilic proteins in biological membranes, using solution of Triton X-114 as an extractant [16,17]. Furthermore, this surfactant has been used for the preconcentration of vitamins A and E without their decomposition. The efficiency extraction with Genapol X-080 for vitamins A and E in blood and serum samples has been shown to be comparable to that obtained using an official method, which validates this method for quantification of the said vitamins in blood samples [18]. Furthermore, surfactant aggregates have been widely used as drug delivery vehicles [19,20] because they have low viscosity, small aggregate size, simple preparation and long shelf-life. In fact, micellar solubilization is one of the most important properties of surfactant solution, widely used in pharmaceutical, food, detergency and cosmetic industries, enhanced oil recovery and so forth [21].