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We constructed a liquid-phase colorimetric biosensor to detect Triglycerides (TG) contamination in water using a Porcine Pancreatic Lipase Immobilized Zinc – chitosan nanocomposite matrix with Phenolsulfonphthalein as the chromophore. The nanoparticle-augmented matrix was characterized using an SEM—the change in the chromophore colour from red to yellow indicated vegetable oil hydrolysis and fatty acid release. The biosensor showed a LOQ between 25–500 µg/mL at an operating temperature between 25–45 °C, over a pH range of 4–9 within 5 minutes. The biosensor showed resilience to samples contaminated up to 50 times the BIS permissible limits for iron, copper and manganese. The sensor showed repeatability of nearly 100% with the LOD 3 µg/mL, sensitivity 47.1 U/µg/cm2 and retained up to 80% of its activity till the 10th day when stored at 10 °C. A fully adept version of the biosensor can be applied to detect TG in water and wastewater.

Background: Photodynamic therapy (PDT) of cancer has been limited by the poor solubility of most photosensitizers, use of high drug dosages, and the pH difference between the tumor tissue microenvironment (slightly acidic) and the bloodstream. These affect cellular uptake, selectivity and singlet oxygen generation. Materials & methods: We formulated Photinia glabra–green synthesized zinc oxide–protoporphyrin IX (PG–ZnO–PP) nanoconjugates by conjugating the ZnO nanoparticles enriched with amino groups and PP. Results: PG–ZnO–PP nanoconjugates showed higher rate of reactive oxygen species generation, improved cellular uptake in the acidic pH and lower IC50 toward Eca-109 cells for PDT. Conclusion: PG–ZnO–PP nanoconjugates are a potential solution to reducing drug dosage of PP through improved drug uptake, for enhanced targetability and reduced skin photosensitivity with improved PDT efficacy. The progress of treating cancer using light-sensitive drugs and laser light of known wavelength has been limited by the poor solubility of most light-sensitive drugs, the use of high drug dosages and the slightly acidic environment within the cancerous tissues compared with normal blood in the body. These affect the ability of drugs to accumulate in cancerous cells, and not the normal cells, and the ability to produce the oxygen species that are toxic to the cancerous cells. In this paper, we prepared nanoparticles from zinc acetate using Photinia glabra (PG) fruit extract which were then used to chemically react with a light-sensitive drug called protoporphyrin IX (PP) to formulate small particles known as PG–zinc oxide (ZnO)–PP nanoconjugates. Our results showed that PG–ZnO–PP nanoconjugates had the ability to produce the toxic oxygen particles at a high rate and in good quantity. They also had a higher capability to accumulate in the cancerous cells at a pH below 7 with lower values of the drug needed to cause 50% of cell death toward the cancerous cells which affect the tube that connects from the throat to the stomach when projected with laser light. We could consider PG–ZnO–PP nanoconjugates to serve as a potential solution for reducing the dosage of PP needed to treat cancer in the presence of laser light, and at the same time they can help to reduce the skin-related side effects for patients after treatment when exposed to light. pH-responsive PG–ZnO–PP nanoconjugates with enhanced cellular uptake in tumor tissue microenvironment which is slightly acidic, and reactive oxygen species and singlet quantum yield with a lower dosage of protoporphyrin IX, for improved photodynamic therapy of cancer, thereby reducing skin photosensitivity. [ABSTRACT FROM AUTHOR]

Abstract Background In the present study, we aimed to develop a novel isotretinoin delivery model for treating skin diseases, revealing its potential advantages in drug delivery and targeted therapy. Using a self-assembly strategy, we grafted a dendrimer, based on a well-defined branched structure for nanomedical devices, with a well-defined nanoarchitecture, yielding spherical, highly homogeneous molecules with multiple surface functionalities. Accordingly, a self-assembled dendrimer-conjugated system was developed to achieve the transdermal delivery of isotretinoin (13cRA-D). Results Herein, 13cRA-D showed remarkable controlled release, characterized by slow release in normal tissues but accelerated release in tissues with low pH, such as sites of inflammation. These release characteristics could abrogate the nonteratogenic side effects of isotretinoin and allow efficient skin permeation. Moreover, 13cRA-D exhibited high therapeutic efficacy in acne models. Based on in vitro and in vivo experimental results, 13cRA-D afforded better skin penetration than isotretinoin and allowed lesion targeting. Additionally, 13cRA-D induced minimal skin irritation. Conclusion Our findings suggest that 13cRA-D is a safe and effective isotretinoin formulation for treating patients with skin disorders. Graphical Abstract

In this study, chitosan nanoparticles (CSNPs) encapsulating Foeniculum vulgare (FV) seed extract (SE) were prepared for the controlled delivery of bioactive phytoconstituents. The prepared CSNPs encapsulating FVSE as sustain-releasing nanoconjugate (CSNPs-FVSE) was used as a potent source of functional metabolites including kaempferol and quercetin for accelerated reclamation of sensory and motor functions following peripheral nerve injury (PNI). The nanoconjugate exhibited in vitro a biphasic diffusion-controlled sustained release of quercetin and kaempferol ensuring prolonged therapeutic effects. The CSNPs-FVSE was administered through gavaging to albino mice daily at a dose rate of 25 mg/kg body weight from the day of induced PNI till the end of the experiment. The conjugate-treatment induced a significant acceleration in the regain of motor functioning, evaluated from the sciatic function index (SFI) and muscle grip strength studies. Further, the hotplate test confirmed a significantly faster recuperation of sensory functions in conjugate-treated group compared to control. An array of underlying biochemical pathways regulates the regeneration under well-optimized glucose and oxidant levels. Therefore, oxidant status (TOS), blood glycemic level and total antioxidant capacity (TAC) were evaluated in the conjugate-treated group and compared with the controls. The treated subjects exhibited controlled oxidative stress and regulated blood sugars compared to the non-treated control. Thus, the nanoconjugate enriched with polyphenolics significantly accelerated the regeneration and recovery of functions after nerve lesions. The biocompatible nanocarriers encapsulating the nontoxic natural bioactive constitutents have great medicinal and economic value.

The development of resistance, instability and high doses are some drawbacks of biologically active natural products. Modification of natural compounds to make it broad spectrum is the standard approach in drug design. This paper sets to modify the naringenin by silver nanoparticle conjugation to enhance its already reported pharmacological activities. The naringenin-nano silver conjugate was synthesized by one-step green synthesis, that is, sunlight exposure confirmed by UV spectroscopy. The biosynthesized naringenin-nanosilver conjugate was tested for antiacanthamoebal and antimicrobial potential. The antibacterial potential was increased by 5.8–6.14 fold against Gram positive bacteria, that is, S. aureus and Bacillus subtilis and 4.5–13.6 fold against Gram negative bacteria, that is, Escherichia coli and Pseudomonas aeruginosa. The standard naringenin-nanosilver conjugate significantly reduced the LC50 values against the Acanthamoeba cells, by, 66% and 36%, as compared to substrate naringin and standard naringenin respectively while biotransformed naringinin-nanosilver conjugate reduced LC50 by 50.56%, compared with biotransformed naringenin. Hence modification of natural product as nanoconjugate is the best practice for improvement as an effective drug. [ABSTRACT FROM AUTHOR]

This study presents the synthesis of some metal {M = Zn(II), Lu(III), Si(IV)} phthalocyanines bearing chlorine and 2-(4-methylthiazol-5-yl) ethoxy groups at peripheral or axial positions. The newly synthesized metal phthalocyanines were characterized by applying FT-IR, 1H NMR, mass, and UV-Vis spectroscopic approaches. Additionally, the surface of gold nanoparticles was modified with zinc(II) and silicon(IV) phthalocyanines. The resultant nanoconjugates were characterized using TEM images. Moreover, the effect of metal ions and position of substituent, and gold nanoparticles on the photochemical and sonophotochemical properties of the studied phthalocyanines was investigated. The highest singlet oxygen quantum yield was obtained for the lutetium phthalocyanine by applying photochemical and sonophotochemical methods. However, the linkage of the zinc(II) and silicon(IV) phthalocyanines to the surface of gold nanoparticles improved significantly their singlet oxygen generation capacities. [ABSTRACT FROM AUTHOR]

The current study was designed to develop a nanoconjugate of cordycepin-melittin (COR-MEL) and assess its healing property in wounded diabetic rats. The prepared nanoconjugate has a particle size of 253.5 ± 17.4 nm with a polydispersity index (PDI) of 0.35 ± 0.04 and zeta potential of 17.2 ± 0.3 mV. To establish the wound healing property of the COR-MEL nanoconjugate, animal studies were pursued, where the animals with diabetes were exposed to excision and treated with COR hydrogel, MEL hydrogel, or COR-MEL nanoconjugate topically. The study demonstrated an accelerated wound contraction in COR-MEL nanoconjugate -treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde (MDA) and exhaustion of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Additionally, the nanoconjugate exhibits a strong expression of transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF)-A, and platelet-derived growth factor (PDGFR)-β, indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1 (Col 1A1). Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Background: In the present study, we aimed to develop a novel isotretinoin delivery model for treating skin diseases, revealing its potential advantages in drug delivery and targeted therapy. Using a self-assembly strategy, we grafted a dendrimer, based on a well-defined branched structure for nanomedical devices, with a well-defined nanoarchitecture, yielding spherical, highly homogeneous molecules with multiple surface functionalities. Accordingly, a self-assembled dendrimer-conjugated system was developed to achieve the transdermal delivery of isotretinoin (13cRA-D). Results: Herein, 13cRA-D showed remarkable controlled release, characterized by slow release in normal tissues but accelerated release in tissues with low pH, such as sites of inflammation. These release characteristics could abrogate the nonteratogenic side effects of isotretinoin and allow efficient skin permeation. Moreover, 13cRA-D exhibited high therapeutic efficacy in acne models. Based on in vitro and in vivo experimental results, 13cRA-D afforded better skin penetration than isotretinoin and allowed lesion targeting. Additionally, 13cRA-D induced minimal skin irritation. Conclusion: Our findings suggest that 13cRA-D is a safe and effective isotretinoin formulation for treating patients with skin disorders. [ABSTRACT FROM AUTHOR]

Background: The tumor microenvironment (TME) provides a conducive environment for the growth and survival of tumors. Negative factors present in TME, such as IL-10, may limit the effectiveness of cellular vaccines based on dendritic cells, therefore, it is important to control its effect. The influence of IL-10 on immune cells can be abolished e.g., by using antibodies against the receptor for this cytokine - anti-IL-10R. Furthermore, the anticancer activity of cellular vaccines can be enhanced by modifying them to produce proinflammatory cytokines, such as IL-12, IL-15 or IL-18. Additionally, an immunomodulatory dose of methotrexate and hydroxyethyl starch (HES-MTX) nanoconjugatemay stimulate effector immune cells and eliminate regulatory T cells, which should enhance the antitumor action of immunotherapy based on DC vaccines. The main aim of our study was to determine whether the HES-MTX administered before immunotherapy with anti-IL-10R antibodies would change the effect of vaccines based on dendritic cells overproducing IL-12, IL-15, or IL-18. Methods: The activity of modified DCs was checked in two therapeutic protocols - immunotherapy with the addition of anti-IL10R antibodies and chemoimmunotherapy with HES-MTX and anti-IL10R antibodies. The inhibition of tumor growth and the effectiveness of the therapy in inducing a specific antitumor response were determined by analyzing lymphoid and myeloid cell populations in tumor nodules, and the activity of restimulated splenocytes. Results and conclusions: Using the HES-MTX nanoconjugate before immunotherapy based on multiple administrations of anti-IL-10R antibodies and cellular vaccines capable of overproducing proinflammatory cytokines IL12, IL-15 or IL-18 created optimal conditions for the effective action of these vaccines in murine colon carcinoma MC38 model. The applied chemoimmunotherapy caused the highest inhibition of tumor growth in the group receiving DC/IL-15/IL-15Rα/TAg + DC/IL-18/TAg at the level of 72.4%. The use of cellular vaccines resulted in cytotoxic activity increase in both immuno- or chemoimmunotherapy. However, the greatest potential was observed both in tumor tissue and splenocytes obtained from mice receiving two- or threecomponent vaccines in the course of combined application. Thus, the designed treatment schedule may be promising in anticancer therapy. [ABSTRACT FROM AUTHOR]

BackgroundThe tumor microenvironment (TME) provides a conducive environment for the growth and survival of tumors. Negative factors present in TME, such as IL-10, may limit the effectiveness of cellular vaccines based on dendritic cells, therefore, it is important to control its effect. The influence of IL-10 on immune cells can be abolished e.g., by using antibodies against the receptor for this cytokine - anti-IL-10R. Furthermore, the anticancer activity of cellular vaccines can be enhanced by modifying them to produce proinflammatory cytokines, such as IL-12, IL-15 or IL-18. Additionally, an immunomodulatory dose of methotrexate and hydroxyethyl starch (HES-MTX) nanoconjugate may stimulate effector immune cells and eliminate regulatory T cells, which should enhance the antitumor action of immunotherapy based on DC vaccines. The main aim of our study was to determine whether the HES-MTX administered before immunotherapy with anti-IL-10R antibodies would change the effect of vaccines based on dendritic cells overproducing IL-12, IL-15, or IL-18.MethodsThe activity of modified DCs was checked in two therapeutic protocols - immunotherapy with the addition of anti-IL10R antibodies and chemoimmunotherapy with HES-MTX and anti-IL10R antibodies. The inhibition of tumor growth and the effectiveness of the therapy in inducing a specific antitumor response were determined by analyzing lymphoid and myeloid cell populations in tumor nodules, and the activity of restimulated splenocytes.Results and conclusionsUsing the HES-MTX nanoconjugate before immunotherapy based on multiple administrations of anti-IL-10R antibodies and cellular vaccines capable of overproducing proinflammatory cytokines IL-12, IL-15 or IL-18 created optimal conditions for the effective action of these vaccines in murine colon carcinoma MC38 model. The applied chemoimmunotherapy caused the highest inhibition of tumor growth in the group receiving DC/IL-15/IL-15Rα/TAg + DC/IL-18/TAg at the level of 72.4%. The use of cellular vaccines resulted in cytotoxic activity increase in both immuno- or chemoimmunotherapy. However, the greatest potential was observed both in tumor tissue and splenocytes obtained from mice receiving two- or three-component vaccines in the course of combined application. Thus, the designed treatment schedule may be promising in anticancer therapy.

Graphene oxide (GO) based nano‐formulation has gained much attention because of its carbonaceous composition with biologically benign properties. In this study, the interactions of GO with tacrine (TAC), an FDA approved Alzheimer's disease (AD) drug, are explored using various analytical tools and theoretical modeling techniques. Furthermore, the modulatory effect of these nano‐conjugates toward the in‐vitro catalytic activity of the neurodegenerative enzyme acetylcholinesterase (AChE) is also quantified. The maximal rate for enzyme inhibition in presence of the nanoconjugate decreases up to an extent of 16 and 34 % in comparison with TAC and GO, respectively. Interestingly, these results are in sharp contrast to the increased AChE activity on adsorption into spherical gold and silver nanoparticles. The current findings demonstrate the synergistic use of TAC−GO hybrid material with augmented AChE inhibition efficacy towards the treatment of Alzheimer's disease (AD). Additionally, GO presents a sustainable alternative for biomedical applications to inorganic equivalents. [ABSTRACT FROM AUTHOR]

The current study was designed to develop a nanoconjugate of cordycepin-melittin (COR-MEL) and assess its healing property in wounded diabetic rats. The prepared nanoconjugate has a particle size of 253.5 ± 17.4 nm with a polydispersity index (PDI) of 0.35 ± 0.04 and zeta potential of 17.2 ± 0.3 mV. To establish the wound healing property of the COR-MEL nanoconjugate, animal studies were pursued, where the animals with diabetes were exposed to excision and treated with COR hydrogel, MEL hydrogel, or COR-MEL nanoconjugate topically. The study demonstrated an accelerated wound contraction in COR-MEL nanoconjugate -treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde (MDA) and exhaustion of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Additionally, the nanoconjugate exhibits a strong expression of transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF)-A, and platelet-derived growth factor (PDGFR)-β, indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1 (Col 1A1). Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms. [ABSTRACT FROM AUTHOR]

Background: Understanding the negative impact of the tumor microenvironment on the creation of an effective immune response has contributed to the development of new therapeutic anti-cancer strategies. One such solution is combined therapy consisting of chemotherapeutic administration followed by dendritic cell (DC)-based vaccines. The use of cytostatic leads to the elimination of cancer cells, but can also modulate the tumor milieu. Moreover, great efforts are being made to increase the therapeutic outcome of immunotherapy, e.g. by enhancing the ability of DCs to generate an efficient immune response, even in the presence of immunosuppressive cytokines such as IL-10. The study aimed to determine the effectiveness of combined therapy with chemotherapeutic with immunomodulatory potential – HES-MTX nanoconjugate (composed of methotrexate (MTX) and hydroxyethyl starch (HES)) and DCs with downregulated expression of IL-10 receptor stimulated with tumor antigens (DC/shIL-10R/TAg) applied in MC38 murine colon carcinoma model. Methods: With the use of lentiviral vectors the DCs with decreased expression of IL-10R were obtained and characterized. During in vivo studies MC38-tumor bearing mice received MTX or HES-MTX nanoconjugate as a sole treatment or combined with DC-based immunotherapy containing unmodified DCs or DCs transduced with shRNA against IL-10R (or control shRNA sequence). Tumor volume was monitored during the experiment. One week after the last injection of DC-based vaccines, tumor nodules and spleens were dissected for ex vivo analysis. The changes in the local and systemic anti-tumor immune response were estimated with the use of flow cytometry and ELISA methods. Results and conclusions: In vitro studies showed that the downregulation of IL)10R expression in DCs enhances their ability to activate the specific anti-tumor immune response. The use of HES-MTX nanoconjugate and DC/shIL-10R/TAg in the therapy of MC38-tumor bearing mice resulted in the greatest tumor growth inhibition. At the local anti-tumor immune response level a decrease in the infiltration of cells with suppressor activity and an increase in the influx of effector cells into MC38 tumor tissue was observed. These changes were crucial to enhance the effective specific immune response at the systemic level, which was revealed in the greatest cytotoxic activity of spleen cells against MC38 cells. [ABSTRACT FROM AUTHOR]

Electron-donating porphyrins (Por), electron-accepting phthalocyanines (Pcs), and reduced graphene oxide (RGO) were integrated into a multicomponent nanoconjugate (Por-RGO-Pc). The donor-π-acceptor nanoconjugate Por-RGO-Pc was characterized using Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), and ultraviolet—visible (UV—Vis) spectroscopy. Photoinduced cascading electron/charge transfer from Por to RGO and from RGO to Pc was established from fluorescence, electrochemical, and femtosecond transient absorption (fs-TA) spectroscopy studies. The increased distance between the electron donors and acceptors of the Por-RGO-Pc nanoconjugate compared to the parent materials and the intermediate RGO-Pc results in long-lived charge separation, and an enhancement in nonlinear optical (NLO) absorption (a large NLO coefficient of about 827.44 cm/GW) towards nanosecond laser irradiation at 532 nm. [ABSTRACT FROM AUTHOR]

Edge-functionalization of graphene is emerging as a powerful chemical method for the construction of π-delocalized highly-planar graphene nanoconjugates that are not accessible through surface-supported syntheses. Herein, a graphene-porphyrin nanoconjugate via a robust pyrazine (pz) linkage has been obtained by condensing 2,3-diamino-5,10,15,20-tetraphenylporphyrin (DA-TPP) with ortho-quinone (o-quinone) moieties at edge sites of graphene oxide (GO). The as-prepared GO-pz-TPP exhibits an intense absorption extending from 375 to 900 nm and a high quenching yield (98%) of fluorescence, indicating a strong electronic coupling effect between GO and TPP units. GO-pz-TPP displays strong nonlinear optical (NLO) absorption and giant NLO coefficients with 800 and 1,030 nm fs laser, in sharp contrast to traditional graphene-porphyrin nanohybrids only NLO-active towards ns laser. Such a dramatic NLO performance towards femtosecond pulsed laser has not been achieved in any carbon-chromophores nanohybridized materials to date. This work validates the π-extended edge-functionalization strategy as a means to tune the NLO properties of graphene, thereby providing a new paradigm for the assembly of versatile optoelectronic materials. [ABSTRACT FROM AUTHOR]

BackgroundUnderstanding the negative impact of the tumor microenvironment on the creation of an effective immune response has contributed to the development of new therapeutic anti-cancer strategies. One such solution is combined therapy consisting of chemotherapeutic administration followed by dendritic cell (DC)-based vaccines. The use of cytostatic leads to the elimination of cancer cells, but can also modulate the tumor milieu. Moreover, great efforts are being made to increase the therapeutic outcome of immunotherapy, e.g. by enhancing the ability of DCs to generate an efficient immune response, even in the presence of immunosuppressive cytokines such as IL-10. The study aimed to determine the effectiveness of combined therapy with chemotherapeutic with immunomodulatory potential – HES-MTX nanoconjugate (composed of methotrexate (MTX) and hydroxyethyl starch (HES)) and DCs with downregulated expression of IL-10 receptor stimulated with tumor antigens (DC/shIL-10R/TAg) applied in MC38 murine colon carcinoma model.MethodsWith the use of lentiviral vectors the DCs with decreased expression of IL-10R were obtained and characterized. During in vivo studies MC38-tumor bearing mice received MTX or HES-MTX nanoconjugate as a sole treatment or combined with DC-based immunotherapy containing unmodified DCs or DCs transduced with shRNA against IL-10R (or control shRNA sequence). Tumor volume was monitored during the experiment. One week after the last injection of DC-based vaccines, tumor nodules and spleens were dissected for ex vivo analysis. The changes in the local and systemic anti-tumor immune response were estimated with the use of flow cytometry and ELISA methods.Results and conclusionsIn vitro studies showed that the downregulation of IL-10R expression in DCs enhances their ability to activate the specific anti-tumor immune response. The use of HES-MTX nanoconjugate and DC/shIL-10R/TAg in the therapy of MC38-tumor bearing mice resulted in the greatest tumor growth inhibition. At the local anti-tumor immune response level a decrease in the infiltration of cells with suppressor activity and an increase in the influx of effector cells into MC38 tumor tissue was observed. These changes were crucial to enhance the effective specific immune response at the systemic level, which was revealed in the greatest cytotoxic activity of spleen cells against MC38 cells.

Preclinical studies suggest that most of statins or 3‑hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors possess pleiotropic anticancer activity. The aim of the present work was to investigate the conjugation of the statin fluvastatin (FLV) with scorpion venom (SV), a natural peptide with proven anticancer properties, to enhance FLV cytotoxic activity and prepare colon targeted FLV-SV nanoconjugate beads for management of colon cancer. Response surface design was applied for the optimization of FLV-SV nanoconjugates. FLV-SV particle size and zeta potential were selected as responses. Cytotoxicity of optimized FLV-SV nanoconjugates was carried out on Caco2 cell line. Colon targeted alginate coated Eudragit S100 (ES100) beads for the optimized formula were prepared with the utilization of barium sulfate (BaSO4) as radiopaque contrast substance. Results revealed that optimized FLV-SV nanoconjugates showed a size of 71.21 nm, while the zeta potential was equal to 29.13 mV. Caco2 cells were considerably more sensitive to the FLV-SV formula (half-maximal inhibitory concentration (IC50) = 11.91 µg/mL) compared to SV and FLV used individually, as shown by values of IC50 equal to 30.23 µg/mL and 47.68 µg/mL, respectively. In vivo imaging of colon targeted beads, carried out by employing real-time X-ray radiography, confirmed the efficiency of colon targeted beads. Overall our results indicate that the optimized FLV-SV nanoconjugate loaded alginate coated ES100 beads could represent a promising approach for colon cancer with efficient colon targeting ability. [ABSTRACT FROM AUTHOR]

Breast cancer is considered as the second major cause of death among women with a high mortality rate worldwide. The exceptionally fast rate of metastasis, the emergence of drug-resistant mechanisms, and the occurrence of inadvertent side effects by cytotoxic chemotherapies often make conventional chemotherapy and immunotherapy treatments ineffective. Similar to other solid tumours, breast cancer can develop unique cellular and molecular characteristics forming an atypical permissive tumour microenvironment (TME). Due to the unique features of TME, cancer cells can further proliferate and coadapt with the stromal cells and evade immunosurveillance. Breast cancer cells aberrantly abundantly express various pieces of molecular machinery (the so-called oncomarkers) in favour of their survival, progression, metastasis, and further invasion. Such overexpressed oncomarkers can be exploited in the detection and targeted therapy of cancer. Among breast cancer oncomarkers, epidermal growth factor receptors, particularly HER2, are considered as clinically valid molecular targets not only for the thorough diagnosis but also for the targeted therapy of the disease using different conventional and advanced nanoscale treatment modalities. This review aims to elaborate on the recent advances in terms of targeted therapy of HER2-positive breast cancer, and discuss various types of multifunctional nanomedicines/theranostics, and antibody-/aptamer-drug conjugates. [ABSTRACT FROM AUTHOR]

Phthalocyanine (Pc) complexes are an important class of dyes with numerous (e.g., biological, photophysical, and analytical) applications. Among the methods used to improve the properties of these complexes, one should mention the introduction of different substituents, variation of the central metal ion, ligand exchange, and conjugation to nanomaterials (e.g., carbon-based nanomaterials and metal nanoparticles (NPs)). This work briefly reviews Pc complex conjugation to Ag and Au NPs, highlights the different NP shapes, and discusses the diversity of conjugation approaches. Moreover, the use of UV–Vis spectroscopy, powder X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering and Fourier transform infrared spectroscopy to characterize Pc-NP hybrids is summarized. The effect of conjugation on Pc photo-physicochemical properties (fluorescence, singlet oxygen generation, triplet state formation, and optical limiting behavior) is discussed, and future perspectives for the synthesis and applications of new hybrids are provided.

Introduction: Methotrexate (MTX) is used as a folic acid antagonist in the treatment of many human cancers. Attachment of hydrophilic ligands to MTX improves its efficacy due to reducing toxicity and enzymatic degradation and it also increases its in-vivo half-life. Materials and Methods: In the present study, pH-responsive nanoconjugates of methoxy poly(ethylene glycol)-glutamic acid methotrexate (mPEG-Glu-MTX) have been prepared and characterized using hydrogen nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FT-IR). Glutamic acid is attached to the mPEG chain by the carboxylic group and to the MTX via an amide bond to the amine group. Results: The prepared nanoconjugate has the mean diameter ranging from 160 to 190 nm and, the drug release was significantly induced two times at the pH of 5.5 and 3.5 compared with pH 7.4 (P < 0.05). The prepared mPEG-Glu-MTX nanoconjugate showed toxicity similar to AGS, MDA, and MCF7 cell lines compared with the free form of MTX (P > 0.1), which indicates that the conjugation does not effect on the MTX cytotoxicity but is expected to be successful in the targeted delivery of MTX. Conclusion: The results show that manufactured nanoconjugates can be considered as an efficient drug delivery system in the treatment of cancer; however, further studies are needed on the targeting activity of this nanocarrier in in-vivo conditions. [ABSTRACT FROM AUTHOR]

Abstract Background The first-line chemotherapy drug that is used to treat pancreatic ductal adenocarcinoma is gemcitabine. Unfortunately, its effectiveness is hampered by its chemo-resistance, low vascularization and drug biodistribution limitations in the tumor microenvironment. Novel nanotherapeutics must be developed in order to improve the prognosis for patients with pancreatic cancer. Results We developed a synthetic methodology for obtaining a water-soluble nanoconjugate of a [60]fullerene-glycine derivative with the FDA-approved drug gemcitabine (nanoC 60 GEM). The proposed synthetic protocol enables a highly water-soluble [60]fullerene-glycine derivative (6) to be obtained, which was next successfully conjugated with gemcitabine using the EDCI/NHS carbodiimide protocol. The desired nanoconjugate was characterized using mass spectrometry and DLS, IR and XPS techniques. The photogeneration of singlet oxygen and the superoxide anion radical were studied by measuring 1O2 near-infrared luminescence at 1270 nm, followed by spin trapping of the DMPO adducts by EPR spectroscopy. The biological assays that were performed indicate that there is an inhibition of the cell cycle in the S phase and the induction of apoptosis by nanoC60GEM. Conclusion In this paper, we present a robust approach for synthesizing a highly water-soluble [60]fullerene nanoconjugate with gemcitabine. The performed biological assays on pancreatic cancer cell lines demonstrated cytotoxic effects of nanoC60GEM, which were enhanced by the generation of reactive oxygen species after blue LED irradiation of synthesized fullerene nanomaterial.

We are investigating the biological and biomedical imaging roles and impacts of fluorescent metallocorrole-TiO2 nanoconjugates as potential near-infrared optical contrast agents in vitro in cancer and normal cell lines. The TiO2 nanoconjugate labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato aluminum(III) (1-Al-TiO2) was prepared. The nanoparticle 1-Al-TiO2 was characterized by transmission electron microscopy (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of three different samples of TiO2 nanoparticles (bare, H2O2 etched, and 1-Al functionalized) showed similarity in shapes and sizes with an average diameter of 29nm for 1-Al-TiO2. Loading of 1-Al on the TiO2 surfaces was determined to be ca. 20-40mg 1-Al/g TiO2. Confocal fluorescence microscopy (CFM) studies of luciferase-transfected primary human glioblastoma U87-Luc cells treated with the nanoconjugate 1-Al-TiO2 as the contrast agent in various concentrations were performed. The CFM images revealed that 1-Al-TiO2 was found inside the cancer cells even at low doses (0.02-2μg/mL) and localized in the cytosol. Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al-TiO2 showed minimal cytotoxic effects even at higher doses (2-2000μg/mL) after 24h. A similar observation was made using primary mouse hepatocytes (PMH) treated with 1-Al-TiO2 at low doses (0.0003-3μg/mL). Longer incubation times (after 48 and 72h for U87-Luc) and higher doses (>20μg/mL 1-Al-TiO2 for U87-Luc and >3μg/mL 1-Al-TiO2 for PMH) showed decreased cell viability.

Different approaches have been utilized to conjugate phthalocyanine complexes to Ag and Au nanoparticles of different shapes and sizes and thus enhance the photo-physicochemical properties of the starting materials. Phthalocyanine (Pc) complexes are an important class of dyes with numerous (e.g., biological, photophysical, and analytical) applications. Among the methods used to improve the properties of these complexes, one should mention the introduction of different substituents, variation of the central metal ion, ligand exchange, and conjugation to nanomaterials (e.g., carbon-based nanomaterials and metal nanoparticles (NPs)). This work briefly reviews Pc complex conjugation to Ag and Au NPs, highlights the different NP shapes, and discusses the diversity of conjugation approaches. Moreover, the use of UV–Vis spectroscopy, powder X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering and Fourier transform infrared spectroscopy to characterize Pc-NP hybrids is summarized. The effect of conjugation on Pc photo-physicochemical properties (fluorescence, singlet oxygen generation, triplet state formation, and optical limiting behavior) is discussed, and future perspectives for the synthesis and applications of new hybrids are provided. [ABSTRACT FROM AUTHOR]

Photodynamic antimicrobial therapy aims to develop disinfecting strategies using light, oxygen and a photosensitizer molecule, to form reactive oxygen species, capable of unspecifically killing bacteria, without the risk of developing antimicrobial resistance. However, most photosensitizers are prone to highly aggregate in aqueous media, diminishing their efficiency. Aiming to avert this, the use of photosensitizers conjugated in bio-based formulations is a topic that has been received with enthusiasm by the scientific community1. In the present work, as part of the project POLYTHEA (http://www.polythea.eu/), we developed a formulation based in acetylated lignin nanoparticles for the transport of five different porphyrin compounds2. The loaded nanoparticles were fully characterized and the nanoparticles were tested against a Gram-negative (Escherichia coli) and a Gram-positive (Staphylococcus aureus) bacteria. Depending on the nature of the photosensitizer (cationic or non-cationic), the nanoparticles were able to affect the survival of E. coli , while most of them were efficient against S. aureus. Interestingly, the formulation attenuated a dark toxicity effect found for the free photosensitizers. The intended formulation was able to be loaded with the five selected photosensitizers, proving to be a versatile nanoconjugate. Furthermore, the formulation was stable and its efficiency against bacteria was demonstrated against model Gram-positive bacteria. Continuous efforts are being made to increase the knowledge on this type of formulation upon encapsulation of other types of photosensitizers (i.e., phthalocyanines, natural compounds, chlorins), while providing an aggregated value to an abundant natural polymer such as lignin. [ABSTRACT FROM AUTHOR]

Ibuprofen is a well-known non-steroidal anti-inflammatory (NSAID) medicine that is often used to treat inflammation in general. When given orally, it produces gastrointestinal issues which lead to lower patient compliance. Ibuprofen transdermal administration improves both patient compliance and the efficacy of the drug. Nanoconjugation hydrogels were proposed as a controlled transdermal delivery tool for ibuprofen. Six formulations were prepared using different compositions including chitosan, lipids, gum arabic, and polyvinyl alcohol, through ionic interaction, maturation, and freeze–thaw methods. The formulations were characterised by size, drug conjugation efficiency, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Further analysis of optimised hydrogels was performed, including X-ray diffraction (XRD), rheology, gel fraction and swelling ability, in vitro drug release, and in vitro macrophage prostaglandin E2 (PGE2) production testing. The effects of ibuprofen’s electrostatic interaction with a lipid or polymer on the physicochemical and dissolution characterisation of ibuprofen hydrogels were evaluated. The results showed that the S3 (with lipid conjugation) hydrogel provided higher conjugation efficiency and prolonged drug release compared with the S6 hydrogel.

To combine the neutron-capturing and photodynamic properties of boron nanoclusters and derivatives of natural chlorins, respectively, in one molecule, conjugate of chlorin e6 methyl ester with cyclen and dioxane and nitrile derivatives of cobalt bis(dicarbollide) were synthesized. The conditions for the purification of compounds by HPLC were selected since the work with natural compounds is complicated by the production of closely related impurities.

Objective(s): The present work deals with the preparation of nanobioconjugates based on the immobilization of cytochrome c (cyt c) on functionalized multi-wall carbon nanotubes (f-MWCNTs). The effect of the nanosupport and the immobilization procedure on the biochemical and structural characteristics of the immobilized protein was investigated. Methods: The MWCNTs were functionalized to provide alkyl chains with different length and terminal functional groups on their surface. The immobilization of cyt c was achieved through physical adsorption and covalent binding. Cyt-c-based nanoconjugates were characterized in terms of peroxidase activity and stability of protein, while UV-visible spectroscopy was used to investigate the structural characteristics of the immobilized protein. Results: The loading of cyt c on f-MWCNTs was effectively achieved, with immobilization yields reaching up to 77%. The peroxidase activity of cyt c was higher in the case of non covalent immobilization compared to that of covalent procedure. Immobilized cyt c exhibited higher thermal stability than the native protein after 24 h incubation at 40oC, while it preserved up to 100% of its initial activity after incubation in the presence of a denaturing agent such as H2O2. No significant changes in the heme microenvironment of cyt c were observed in the presence of f-MWCNTs. Conclusions: This study has demonstrated that f-MWCNTs are effective supports for the immobilization of cyt c, providing a universally applicable platform for the development of bionanoconjugates with potential use in a wide variety of fields in nanobiocatalysis, biosensing and nanomedicine.

Abstract Background Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. Methods The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Results Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Conclusions Despite the recent licensure of the CYD-TDV dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.

Darshini Shah, Reema Savaliya, Pal Patel, Krupa Kansara, Alok Pandya, Alok Dhawan, Sanjay Singh Institute of Life Sciences, School of Science and Technology, Ahmedabad University, Ahmedabad, Gujarat, India Abstract: Curcumin has a broad spectrum of pharmacological activities, one of them is anticancer activity that is mediated through multiple mechanisms. The major disadvantage associated with the use of curcumin is its low bioavailability due to its poor aqueous solubility. Nanoformulations of curcumin provide an effective solution for this problem. In this study, we have synthesized curcumin Ag nanoconjugates and evaluated their anticancer potential. Keywords: curcumin, anticancer, nanoconjugate, AgNPs

Background: The first-line chemotherapy drug that is used to treat pancreatic ductal adenocarcinoma is gemcitabine. Unfortunately, its effectiveness is hampered by its chemo-resistance, low vascularization and drug biodistribution limitations in the tumor microenvironment. Novel nanotherapeutics must be developed in order to improve the prognosis for patients with pancreatic cancer. Results: We developed a synthetic methodology for obtaining a water-soluble nanoconjugate of a [60]fullerene-glycine derivative with the FDA-approved drug gemcitabine (nanoC60GEM). The proposed synthetic protocol enables a highly water-soluble [60]fullerene-glycine derivative (6) to be obtained, which was next successfully conjugated with gemcitabine using the EDCI/NHS carbodiimide protocol. The desired nanoconjugate was characterized using mass spectrometry and DLS, IR and XPS techniques. The photogeneration of singlet oxygen and the superoxide anion radical were studied by measuring 1O2 near-infrared luminescence at 1270 nm, followed by spin trapping of the DMPO adducts by EPR spectroscopy. The biological assays that were performed indicate that there is an inhibition of the cell cycle in the S phase and the induction of apoptosis by nanoC60GEM. Conclusion: In this paper, we present a robust approach for synthesizing a highly water-soluble [60]fullerene nanoconjugate with gemcitabine. The performed biological assays on pancreatic cancer cell lines demonstrated cytotoxic effects of nanoC60GEM, which were enhanced by the generation of reactive oxygen species after blue LED irradiation of synthesized fullerene nanomaterial. [ABSTRACT FROM AUTHOR]

Conjugation of photosensitizers (PS) with nanoparticles has been largely used as a strategy to stabilize PS in the biological medium resulting in photosensitizing nanoparticles of enhanced photoactivity. Herein, (Meso-5, 10, 15, 20-tetrakis (3-hydroxyphenyl) phorphyryn (mTHPP) was conjugated with diamond nanoparticles (ND) by covalent bond. Nanoconjugate ND-mTHPP showed suitable stability in aqueous suspension with 58 nm of hydrodynamic diameter and Zeta potential of −23 mV. The antibacterial activity of ND-mTHPP was evaluated against Escherichia coli for different incubation times (0–24 h). The optimal activity was observed after 2 h of incubation and irradiation (660 nm; 51 J/cm2) performed right after the addition of ND-mTHPP (100 μg/mL) to the bacterial suspension. The inhibitory activity was 56% whereas ampicillin at the same conditions provided only 14% of bacterial growth inhibition. SEM images showed agglomerate of ND-mTHPP adsorbed on the bacterial cell wall, suggesting that the antimicrobial activity of ND-mTHPP was afforded by inducing membrane damage. Cytotoxicity against murine embryonic fibroblast cells (MEF) was also evaluated and ND-mTHPP was shown to be noncytotoxic since viability of cells cultured for 24 h in the presence of the nanoconjugate (100 μg/mL) was 78%. Considering the enhanced antibacterial activity and the absence of cytotoxic effect, it is possible to consider the ND-mTHPP nanoconjugate as promising platform for application in antimicrobial photodynamic therapy (aPDT).

Cisplatin metallodrugs have been widely used in the treatment of multiple cancers over the last years. Nevertheless, its limited effectiveness, development of acquired drug resistances, and toxic effects decrease nowadays their application in clinical settings. Aiming at improving their features, investigations have been oriented towards the coupling of cisplatin to nanocarriers, like liposomes or inorganic nanoparticles. Moreover, these systems can be further developed to allow targeted co-delivery of drugs. In this review, we describe the major nanosystems and the optimal analytical strategies for their assessment. Finally, we describe the main biological effects of these metallodrug conjugates and the available approaches for their study. [Display omitted] • A way to overcome cisplatin limitations in chemotherapy include the use of nanotransporters. • The most advantageous nanoformulations, particularly those of clinical use, are revisited here. • A plethora of bioanalytical tools for the evaluation of these nanodrug delivery systems is required. • They include the assessment of the synthetic product, evaluation of the in-vitro mode of action and in-vivo application. • In some cases, the design of bioanalytical strategies "fitted to purpose" is also required, as highlighted. [ABSTRACT FROM AUTHOR]

Aim: Chloroquine (Chl) has shown its potential in cancer therapy and graphene oxide (GO) exhibited excellent tumor-targeting ability, biocompatibility and low toxicity. We have endeavored to conjugate Chl to GO sheets and investigated the nonproliferation action on A549 cell lines along with cell signaling pathways. Materials & methods: Cellular toxicity, autophagic flux modulation and cell death mechanism induced by GO–Chl have been investigated on A549 cell lines. Results & conclusion: GO–Chl induces accumulation of autophagosomes (monodansylcadaverine staining, green fluorescence protein-tagged LC3 plasmid and transmission electron microscopy observations) in A549 cells through the blockade of autophagic flux that serves as scaffold for necrosome assembling and activates necroptotic cell death. GO–Chl nanoconjugate could be used as an effective cancer therapeutic agent, by targeting the autophagy necroptosis axis. [ABSTRACT FROM AUTHOR]

Our aim was to develop multiwalled carbon nanotubes (MWCNTs)-based nanoconstructs for the codelivery of N -desmethyl tamoxifen (N-TAM) and a mild P-gp efflux inhibitor, i.e. , quercetin (QT) to treat multiple drug resistant (MDR) cancer cells. The hypothesis banks on three-tier attack on the MDR mechanisms viz. drug derivatization, MWCNT permeation and P-gp inhibition. Tamoxifen was converted to N-TAM and was conjugated to carboxylated MWCNTs mediated by a biodegradable linker, i.e. , tetraethylene glycol (TEG). QT was adsorbed on the conjugate to fetch the final product, i.e. , N- TAM-TEG-MWCNT-QT. Spectroscopic analysis confirmed successful conjugation of N-TAM and physical adsorption of QT. The in-vitro release of N-TAM from the N-TAM-TEG-MWCNT conjugate was minimal to that of pure drug under physiological conditions, but markedly enhanced under the acidic pH of cancer cells. The developed nanometeric formulation was found to be haemo-compatible. Reduced IC 50 values and better cellular uptake in drug resistant MDA-MB-231 cells were observed, followed by enhanced drug availability in the systemic circulation of rodents vis-à-vis naïve drug. The smart nanosystem conferred the desired temporal drug delivery, enhanced drug efficacy, biocompatibility and conducive pharmacokinetics, which are the crucial desired attributes to tackle the increasing concern of MDR in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

A novel series of pyrrolidinonyl metal phthalocyanines (PyMPc, M=Zn, Cu, Co and Ni) was synthesized. Their structures were characterized by IR, 1 H NMR, ESI-MS as well as elemental analysis. The photophysical properties of PyMPcs were studied by UV/vis and fluorescence spectroscopic methods. AuNPs-MPEG-PyMPc nanoconjugates were prepared by conjugating the thiolatedmethoxypolyethylene glycol capped gold nanoparticles (AuNPs-MPEG) with PyMPc through a donor-acceptor interaction. UV/Vis spectra and TEM images evidenced that the PyMPcs were conjugated with gold nanoparticles. The photophysical properties of both free PyMPcs and AuNPs-MPEG-PyMPc nanoconjugates exhibited central ions dependence. PyZnPc and AuNPs-MPEG-PyZnPc exhibited the highest fluorescence quantum yields. But the fluorescence lifetimes of AuNPs-MPEG-PyMPc (M=Cu, Co and Ni) were longer than that of corresponding free phthalocyanines. [ABSTRACT FROM AUTHOR]

Nanoconjugations have been demonstrated to be a dominant strategy for drug delivery and biomedical applications. In this review, we intend to describe several strategies for drug formulation, especially to improve the bioavailability of poorly water-soluble molecules for future application in the therapy of numerous diseases. The context of current studies will give readers an overview of the conjugation strategies for fabricating nanoparticles, which have expanded from conjugated materials to the surface conjugation of nanovehicles. Moreover, nanoconjugates for theranostics are also discussed and highlighted. Overall, these state-of-the-art conjugation methods and these techniques and applications for nanoparticulate systems of poorly water-soluble drugs will inspire scientists to explore and discover more productive techniques and methodologies for drug development.

Background: Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. Methods: The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multiwalled carbon nanotubes (MWNT) with recombinant dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Results: Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Conclusions: Despite the recent licensure of the CYD-TDV dengue vaccine in some countries, results from the vaccine's phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) which is one of the longest-used cytostatics, belongs to the group of antimetabolites and is used for treatment in different types of cancer as well as during autoimmune diseases. MTX can act as a modulator enable to create the optimal environment to generate the specific anti-tumor immune response. A novel system for MTX delivery is its conjugation with high-molecular-weight carriers such as hydroxyethyl starch (HES), a modified amylopectin-based polymer applied in medicine as a colloidal plasma volume expander. Such modification prolongs the plasma half-life of the HES-MTX nanoconjugate and improves the distribution of the drug in the body. In the current study, we focused on evaluating the dose-dependent therapeutic efficacy of chemotherapy with HES-MTX nanoconjugate compared to the free form of MTX, and examining the time-dependent changes in the local and systemic anti-tumor immune response induced by this therapy. To confirm the higher effectiveness of HES-MTX in comparison to MTX, we analyzed its action using murine MC38 colon carcinoma and B16 F0 melanoma tumor models. It was noted that HES-MTX at a dose of 20 mg/kg b.w. was more effective in tumor growth inhibition than MTX in both tumor models. One of the main differences between the two analyzed tumor models concerned the kinetics of the appearance of the immunomodulation. In MC38 tumors, the beneficial change in the tumor microenvironment (TME) landscape, manifested by the depletion of pro-tumor immune cells, and increased influx of cells with strong anti-tumor activity was noted already 3 days after HES-MTX administration, while in B16 F0 model, these changes occurred 10 days after the start of therapy. Thus, the immunomodulatory potential of the HES-MTX nanoconjugate may be closely related to the specific immune cell composition of the TME, which combined with additional treatment such as immunotherapies, would enhance the therapeutic potential of the nanoconjugate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (AJCR Copyright © 2023.)

In photodynamic therapy (PDT), chlorin e6 (Ce6), with its high phototoxic potential and strong absorption of visible light, penetrates deeply into photodamaged tissue. However, despite this fact, the direct application of Ce6 to PDT has been limited by its low water solubility and poor cancer cell localization. To ameliorate this situation, we report herein on the use of a hydrophilic nanoconjugate (DC) comprised of Ce6 and poly(amidoamine) dendrimer, which improves the water solubility and intracellular uptake of Ce6, thereby enhancing PDT efficacy. The synthesis of DC was verified by 1H nuclear magnetic resonance (NMR) analysis, and the coupling ratio of Ce6 introduced onto DC was 2.64. The prepared DC was spherical, with an average diameter of 61.7 ± 3.5 nm. In addition, the characteristic ultraviolet-visible absorption bands of DC in distilled water were similar to those of free Ce6 in dimethyl sulfoxide (DMSO), indicating that the Ce6 chromophore did not change upon conjugation. Investigation using fluorescence spectroscopy and confocal microscopy revealed a greater intracellular uptake of DC than of Ce6 alone. Moreover, DC exhibited significantly increased phototoxicity to human cervical cancer cells, mostly because of apoptotic cell death. These results imply that DC is a candidate for the clinical treatment of PDT.

Reducing antibiotic pollution in the environment in essential to preserve the effectiveness of the available antibiotics. In the present study, β-lactamase from Bacillus tropicus EMB20 was immobilized onto magnetic nanoparticles (Fe 3 O 4) through covalent coupling method. The nanoconjugate was structurally characterized using SEM, FTIR, UV-spectrometry, and XRD diffraction analyses. The prepared enzyme nanoconjugate was thereafter used for remediation of meropenem (Mer) and showed complete removal of 10 mgL−1 Mer within 3 h of treatment. Moreover, the immobilized enzyme was successfully recovered and reused for up to 5 cycles with 57% removal efficiency. The immobilized preparation was also observed to be effective in the removal of higher Mer concentrations of 25 and 50 mgL−1 with 79% and 75% removal efficiency, respectively. The major hydrolyzed product of Mer was found to be opened-lactam ring structure with m/z 402.16. The hydrolyzed product(s) were observed to be non-toxic as revealed through microbial MTT, confocal microscopy, and growth studies. Under the mixed conditions of 50 mgL−1 ampicillin (Amp), 10 mgL−1 amoxicillin (Amox) and, Mer, the nanoconjugate showed simultaneous complete removal of Amp and Mer, while 49% Amox removal was detected after 3 h of treatment. Moreover, the nanoconjugates also showed concomitant complete removal of antibiotic mixture with in 2 h from aquaculture wastewater. Overall, the study comes out with an efficient approach for remediation of β-lactam antibiotics from contaminated systems. [Display omitted] • Bacillus tropicus EMB20 β-lactamase was immobilized on magnetic nanoparticles. • Immobilization efficiency of the nanoconjugate was determined to be 50.3%. • Nanoconjugate catalysed 89% of 10 mgL−1 Mer in 1 h of treatment. • The enzymatic hydrolysis pathway of meropenem was proposed. • The Mer hydrolyzed products were characterized for antibacterial activity and toxicity. [ABSTRACT FROM AUTHOR]

We are investigating the biological and biomedical imaging roles and impacts of fluorescent metallocorrole–TiO 2 nanoconjugates as potential near-infrared optical contrast agents in vitro in cancer and normal cell lines. The TiO 2 nanoconjugate labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato aluminum(III) ( 1-Al –TiO 2 ) was prepared. The nanoparticle 1-Al –TiO 2 was characterized by transmission electron microscopy (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of three different samples of TiO 2 nanoparticles (bare, H 2 O 2 etched, and 1-Al functionalized) showed similarity in shapes and sizes with an average diameter of 29 nm for 1-Al –TiO 2 . Loading of 1-Al on the TiO 2 surfaces was determined to be ca. 20–40 mg 1-Al /g TiO 2 . Confocal fluorescence microscopy (CFM) studies of luciferase-transfected primary human glioblastoma U87-Luc cells treated with the nanoconjugate 1-Al –TiO 2 as the contrast agent in various concentrations were performed. The CFM images revealed that 1-Al –TiO 2 was found inside the cancer cells even at low doses (0.02–2 μg/mL) and localized in the cytosol. Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al –TiO 2 showed minimal cytotoxic effects even at higher doses (2–2000 μg/mL) after 24 h. A similar observation was made using primary mouse hepatocytes (PMH) treated with 1-Al –TiO 2 at low doses (0.0003–3 μg/mL). Longer incubation times (after 48 and 72 h for U87-Luc) and higher doses (> 20 μg/mL 1-Al –TiO 2 for U87-Luc and > 3 μg/mL 1-Al –TiO 2 for PMH) showed decreased cell viability. [ABSTRACT FROM AUTHOR]

Controlled release formulation of pesticides is highly desirable for attaining the most effective utilization of the pesticide as well as reducing environmental pollution. Nano-sized controlled release formulations can provide better penetration through cuticle and deliver the active ingredients efficiently to the targeted tissue. In this study, a novel strategy for the preparation of a nanoconjugate derived from kasugamycin with amino-modified silica was developed. The kasugamycin was connected with amino-modified silica matrix by an amide bond, which could avoid the initial burst release effectively and prolong the duration remarkably. The results showed the kasuga-silica can protect kasugamycin against photo-degradation effectively and the release rate of the active ingredient of nanoconjugate was related to the temperature, pH value, and the particle size (52.5-315.4 nm). With reduced particle size as well as increased temperature and acidity, the release of the active ingredient was faster. This amide linkage of kasuga-silica could be degraded by amidase effectively. This nanoconjugate displayed a better and a sustained bactericidal efficacy against E. coli than kasugamycin technical, which makes it a potential candidate as a controlled release conjugate for kasugamycin in the future. [ABSTRACT FROM AUTHOR]

The present paper describes the synthesis, characterization, and utilization of multi-functional magnetic conjugates that integrate optical and magnetic properties in a single structure for use in many biomedical applications. Spontaneous interaction with eukaryotic cell membrane (HEK-239 cell culture) was determined using fluorescence microscopy, and fluorescence analyses. Both, differences in excitation, and emission wavelength were observed, caused by glutathione intake by cells, resulting in disintegration of core-shell structure of quantum dots, as well as adhesion of conjugate onto cell surface. When compared with quantum dots fluorescent properties, HEK-239 cells with incorporated nanoconjugate exhibited two excitation maxima ( λ = 430 and 390 nm). Simultaneously, application of ideal λ for quantum dots ( λ = 430 nm), resulted in two emission maxima ( λ = 740 and 750 nm). This nanoconjugate fulfills the requirements of term theranostics, because it can be further functionalized with biomolecules as DNA, proteins, peptides or antibodies, and thus serves as a tool for therapy in combination with simultaneous treatment. [ABSTRACT FROM AUTHOR]

Poly-L-lysine (PLL) dendrimers are currently being investigated as antiangiogenic agent for therapy of cancer. In this study, we report folate conjugated poly-L-lysine dendrimers (FPLL) as an efficient carrier for model anticancer drug, doxorubicin hydrochloride (Dox); for pH sensitive drug release, selective targeting to cancer cells, anticancer activity and antiangiogenic activity. This nanoconjugate of Dox showed initial rapid in vitro release followed by gradual slow release, and the drug release was found to be pH sensitive with greater release at acidic pH. In the CAM assay and tubule formation assay with HUVEC, Dox-FPLL formulation showed the significant antiangiogenic activity confirming that activity of PLL was not compromised by the presence of Dox and folic acid. The ex vivo investigations with human breast cancer cell lines MCF-7 showed enhanced cytotoxicity of Dox-FPLL with significantly enhanced intracellular uptake (p < 0.001). The in vivo therapeutic potential of nanoconjugate was determined in MCF-7 breast cancer xenograft model in tumor-bearing mice. Dox-FPLL increased the concentration of Dox in tumor by 121.5-fold after 24 h in comparison with free Dox formulation. The folate conjugated dendrimeric Dox showed superior anti-tumor activity in tumor xenograft model with significantly prolonged survival determined by Kaplan Meier survival analysis (p < 0.001). [ABSTRACT FROM AUTHOR]

Folate-targeted drug delivery has become an alternative therapy for the treatment of various cancers. Folate receptors are known to be responsible for cellular accumulation of folate and folate analogs with high binding affinity. The anthracycline antibiotic doxorubicin has a broad spectrum of antineoplastic action and a correspondingly widespread degree of clinical use. In this work, we aimed to prepare a folate receptor-targeted doxorubicin delivery system to achieve minimal effect of doxorubicin on healthy cells and more cytotoxicity of it on tumor cells. Folate–poly(ethylene glycol)–doxorubicin (FOL-PEG-DOX) nanoconjugate was synthesized through this aim and characterized with nuclear magnetic resonance (NMR), zetasizer, and atomic force microscopy (AFM). Doxorubicin release studies were also performed in vitro. The size of FOL-PEG-DOX was 78.84 nm. The results indicated that doxorubicin release rate from the conjugate was faster at pH 5.0 than pH 7.4 and the amide bond between DOX and PEG was more stable at pH 7.4 than pH 5.0. As a consequence, FOL-PEG-DOX nanoconjugate could be a potentially useful delivery system for folate receptor-positive cancer cells. [ABSTRACT FROM PUBLISHER]