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Abstract TRPV6 calcium channel is a prospective target in prostate cancer (PCa) since it is not expressed in healthy prostate while its expression increases during cancer progression. Despite the role of TRPV6 in PCa cell survival and apoptotic resistance has been already established, no reliable tool to target TRPV6 channel in vivo and thus to reduce tumor burden is known to date. Here we report the generation of mouse monoclonal antibody mAb82 raised against extracellular epitope of the pore region of the channel. mAb82 inhibited TRPV6 currents by 90% at 24 µg/ml in a dose-dependent manner while decreasing store-operated calcium entry to 56% at only 2.4 µg/ml. mAb82 decreased PCa survival rate in vitro by 71% at 12 µg/ml via inducing cell death through the apoptosis cascade via activation of the protease calpain, following bax activation, mitochondria enlargement, and loss of cristae, Cyt C release, pro-caspase 9 cleavage with the subsequent activation of caspases 3/7. In vivo, mice bearing either PC3M trpv6+/+ or PC3M trpv6-/- +pTRPV6 tumors were successfully treated with mAb82 at the dose as low as 100 µg/kg resulting in a significant reduction tumor growth by 31% and 90%, respectively. The survival rate was markedly improved by 3.5 times in mice treated with mAb82 in PC3M trpv6+/+ tumor group and completely restored in PC3M trpv6-/- +pTRPV6 tumor group. mAb82 showed a TRPV6-expression dependent organ distribution and virtually no toxicity in the same way as mAbAU1, a control antibody of the same Ig2a isotype. Overall, our data demonstrate for the first time the use of an anti-TRPV6 monoclonal antibody in vitro and in vivo in the treatment of the TRPV6-expressing PCa tumors.

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Diabetes poses major economic, social, and public health challenges in all countries worldwide. Besides cardiovascular disease and microangiopathy, diabetes is a leading cause of foot ulcers and lower limb amputations. With the continued rise of diabetes prevalence, it is expected that the future burden of diabetes complications, early mortality, and disabilities will increase. The diabetes epidemic is partly caused by the current lack of clinical imaging diagnostic tools, the timely monitoring of insulin secretion and insulin-expressing cell mass (beta (β)-cells), and the lack of patients’ adherence to treatment, because some drugs are not tolerated or invasively administrated. In addition to this, there is a lack of efficient topical treatment capable of stopping the progression of disabilities, in particular for treating foot ulcers. In this context, polymer-based nanostructures garnered significant interest due to their tunable physicochemical characteristics, rich diversity, and biocompatibility. This review article emphasizes the last advances and discusses the prospects in the use of polymeric materials as nanocarriers for β-cell imaging and non-invasive drug delivery of insulin and antidiabetic drugs in the management of blood glucose and foot ulcers.

Improvement of insulin secretion by pancreatic β-cells and preservation of their mass are the current challenges that future antidiabetic drugs should meet for achieving efficient and long-term glycemic control in patients with type 2 diabetes (T2D). The successful development of glucagon-like peptide 1 (GLP-1) analogues, derived from the saliva of a lizard from the Helodermatidae family, has provided the proof of concept that antidiabetic drugs directly targeting pancreatic β-cells can emerge from venomous animals. The literature reporting on the antidiabetic effects of medicinal plants suggests that they contain some promising active substances such as polyphenols and alkaloids, which could be active as insulin secretagogues and β-cell protectors. In this review, we discuss the potential of several polyphenols, alkaloids and venom peptides from snake, frogs, scorpions and cone snails. These molecules could contribute to the development of new efficient antidiabetic medicines targeting β-cells, which would tackle the progression of the disease.

Bioactive aminooxime ligands based on optically pure (R)-limonene have been synthesized in two steps. Their ruthenium (II) cationic water-soluble complex was prepared by a reaction between dichloro (para-cymene) ruthenium (II) dimers and aminooxime ligands in a 1:2 molar ratio. Antibacterial and antibiofilm activities of the synthetized complex were assessed against Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis. The results revealed that the ruthenium (II) complex has higher antibacterial and antibiofilm activities in comparison with free ligands or the enantiopure (R)-limonene. Moreover, microencapsulation of this complex reduced its cytotoxicity and improved their minimum inhibitory concentration and antibiofilm activity toward the considered bacteria. The ruthenium (II) complex targets the bacterial cell membrane, which leads to rapid leakage of intracellular potassium. Our study suggests that the developed ruthenium (II) complexes could be useful as an alternative to conventional disinfectants.

Photoreduction of hexavalent chromium, Cr(VI), identified as carcinogenic and mutagenic element, to Cr(III), believed to be an essential element, using copper sulfide nanostructures (CuS NSs) as photocatalyst was investigated under visible light irradiation (λ > 420 nm). The CuS NSs were synthesized at low temperature using a wet chemical route and fully characterized using various techniques such as scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy and UV–vis spectrophotometry. The photocatalytic reduction of Cr(VI) using visible light irradiation was assessed by UV–vis by following the decrease of the characteristic absorbance at ∼352 nm in the presence of CuS NSs. While CuS NSs promoted Cr(VI) full reduction within 60 min, addition of adipic acid or formic acid accelerated significantly the photocatalytic reduction process. Under optimized conditions, CuS NSs rapidly (12 min) reduced Cr(VI) in presence of 0.5 mM adipic acid. Similarly, Cu NSs were found to be efficient for Cr(VI) reduction dissolved in water from a local lake. Stability studies showed that the photocatalyst could be recycled up to four times without any apparent decrease of its catalytic performance. Keywords: CuS nanostructures, Cr(VI), Photoreduction, Visible light, Lake water

Dermaseptin B2 (DRS-B2) is an antimicrobial peptide secreted by Phyllomedusa bicolor, which is an Amazonian tree frog. Here, we show that the adsorption of DRS-B2 on alginate nanoparticles (Alg NPs) results in a formulation (Alg NPs + DRS-B2) with a remarkable antibacterial activity against Escherichia coli ATCC 8739 and E. coli 184 strains, which are sensitive and resistant, respectively, to colistin. The antibacterial activity, obtained with this new formulation, is higher than that obtained with DRS-B2 alone. Of note, the addition of lactic acid or menthol to this new formulation augments its antibacterial activity against the aforementioned Gram-negative bacilli. The safety of DRS-B2, and also that of the new formulation supplemented or not with a small molecule such as lactic acid or menthol has been proven on the human erythrocytes and the eukaryotic cell line types HT29 (human) and IPEC-1 (animal). Similarly, their stability was determined under the conditions mimicking the gastrointestinal tract with different conditions: pH, temperature, and the presence of digestive enzymes. Based on all the obtained data, we assume that these new formulations are promising and could be suggested, after in vivo approval and completing regulation aspects, as alternatives to antibiotics to fight infections caused by Gram-negative bacilli such as E. coli.

Bacterial resistance to antibiotics has become a major public health problem worldwide, with the yearly number of deaths exceeding 700,000. To face this well-acknowledged threat, new molecules and therapeutic methods are considered. In this context, the application of nanotechnology to fight bacterial infection represents a viable approach and has experienced tremendous developments in the last decades. Escherichia coli (E. coli) is responsible for severe diarrhea, notably in the breeding sector, and especially in pig farming. The resulting infection (named colibacillosis) occurs in young piglets and could lead to important economic losses. Here, we report the design of several new formulations based on colistin loaded on alginate nanoparticles (Alg NPs) in the absence, but also in the presence, of small molecules, such as components of essential oils, polyamines, and lactic acid. These new formulations, which are made by concomitantly binding colistin and small molecules to Alg NPs, were successfully tested against E. coli 184, a strain resistant to colistin. When colistin was associated with Alg NPs, the minimal inhibition concentration (MIC) decreased from 8 to 1 µg/mL. It is notable that when menthol or lactic acid was co-loaded with colistin on Alg NPs, the MIC of colistin drastically decreased, reaching 0.31 or 0.62 µg/mL, respectively. These novel bactericidal formulations, whose innocuity towards eukaryotic HT-29 cells was established in vitro, are presumed to permeabilize the bacterial membrane and provoke the leakage of intracellular proteins. Our findings revealed the potentiating effect of the Alg NPs on colistin, but also of the small molecules mentioned above. Such ecological and economical formulations are easy to produce and could be proposed, after confirmation by in vivo and toxicology tests, as therapeutic strategies to replace fading antibiotics.

The synthesis of multifunctional photothermal nanoagents for antibiotic loading and release remains a challenging task in nanomedicine. Herein, we investigated a simple, low-cost strategy for the preparation of CuS-BSA nanoparticles (NPs) loaded with a natural enzyme, lysozyme, as an antibacterial drug model under physiological conditions. The successful development of CuS-BSA NPs was confirmed by various characterization tools such as transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). Lysozyme loading onto CuS-BSA NPs was evaluated by UV/vis absorption spectroscopy, Fourier-transform infrared spectroscopy (FTIR), zeta potential, and dynamic light scattering measurements. The CuS-BSA/lysozyme nanocomposite was investigated as an effective means for bacterial elimination of B. subtilis (Gram-positive) and E. coli (Gram-negative), owing to the combined photothermal heating performance of CuS-BSA and lysozyme release under 980 nm (0.7 W cm−2) illumination, which enhances the antibiotic action of the enzyme. Besides the photothermal properties, CuS-BSA/lysozyme nanocomposite possesses photodynamic activity induced by NIR illumination, which further improves its bacterial killing efficiency. The biocompatibility of CuS-BSA and CuS-BSA/Lysozyme was elicited in vitro on HeLa and U-87 MG cancer cell lines, and immortalized human hepatocyte (IHH) cell line. Considering these advantages, CuS-BSA NPs can be used as a suitable drug carrier and hold promise to overcome the limitations of traditional antibiotic therapy.

Vaccination remains one of the most effective tools to prevent infectious diseases. To ensure that the best possible antigenic components are chosen to stimulate a cognitive immune response, boosting antigen presentation using adjuvants is common practice. Nanodiamond-based adjuvants are proposed here as a rapid and versatile platform for antigen conjugation, utilizing peptides common to different pathogenic strains and making this strategy a good candidate for a “ready-to-use” vaccine. Initiation of an inflammatory reaction with a resulting immune response is based on the ability of living organisms to entrap nanostructures such as nanodiamonds with neutrophil extracellular traps (NETs) formation. In this work, coronavirus peptide homological for MERS-CoV, fusion inhibitor, was conjugated to nanodiamonds and used to induce neutrophilic-driven self-limiting inflammation. The resulting adjuvant was safe and did not induce any tissue damage at the site of injection. Mice immunization resulted in IgG titers of ¼,000 within 28 days. Immunization of rabbits resulted in the formation of a high level of antibodies persistently present for up to 120 days after the first immunization (animal lifespan ~3 years). The peptide used for immunization proved to be reactive with sera of convalescent COVID patients, demonstrating the possibility of developing pancoronaviral vaccine candidates.

Background: The main goals of cancer treatment are not only to eradicate the tumor itself but also to elicit a specific immune response that overcomes the resistance of tumor cells against chemo- and radiotherapies. Hyperthermia was demonstrated to chemo- and radio-sensitize cancerous cells. Many reports have confirmed the immunostimulatory effect of such multi-modal routines. Methods: We evaluated the interaction of graphene oxide (GO) nanosheets; its derivatives reduced GO and PEGylated rGO, with components of peripheral blood and evaluated its thermal conductivity to induce cell death by localized hyperthermia. Results: We confirmed the sterility and biocompatibility of the graphene nanomaterials and demonstrated that hyperthermia applied alone or in the combination with radiotherapy induced much more cell death in tumor cells than irradiation alone. Cell death was confirmed by the release of lactate dehydrogenase from dead and dying tumor cells. Conclusion: Biocompatible GO and its derivatives can be successfully used in graphene-induced hyperthermia to elicit tumor cell death.

Multivalent interactions are omnipresent in biology and confer biological systems with dramatically enhanced affinities towards different receptors. Such multivalent binding interactions have lately been considered for the development of new therapeutic strategies against bacterial and viral infections. Multivalent polymers, dendrimers, and liposomes have successfully targeted pathogenic interactions. While a high synthetic effort was often needed for the development of such therapeutics, the integration of multiple ligands onto nanostructures turned to be a viable alternative. Particles modified with multiple ligands have the additional advantage of creating a high local concentration of binding molecules. This review article will summarize the different nanoparticle-based approaches currently available for the treatment of viral infections.

Silver nanoparticles (Ag NPs) exhibit antibacterial activity and are extensively used in numerous applications. The aim of this study was to examine the toxic effect of Ag NPs on the marine microalga, Chlorella vulgaris. The microalgae, at the exponential growth phase, were treated with different concentrations of Ag NPs (50 and 100 nm) for 96 h. X-Ray diffraction (XRD) results indicated that the used NPs are single and pure Ag phase with a mean crystallite size of 21 and 32 nm. Ag NPs were found to have a negative effect on viable cell concentration, a variable effect on chlorophyll a concentration, and increased ROS formation. Transmission electron microscopy (TEM) analysis revealed that Ag NPs were present inside the microalgae cells and formed large aggregates in the culture medium. Ag+ ions, in the form of AgNO3, were also assessed at higher concentrations and found to cause inhibitory effects.

Impaired penetration of antibiotics through bacterial biofilms is one of the reasons for failure of antimicrobial therapy. Hindered drug diffusion is caused on the one hand by interactions with the sticky biofilm matrix and on the other hand by the fact that bacterial cells are organized in densely packed clusters of cells. Binding interactions with the biofilm matrix can be avoided by encapsulating the antibiotics into nanocarriers, while interfering with the integrity of the dense cell clusters can enhance drug transport deep into the biofilm. Vapor nanobubbles (VNB), generated from laser irradiated nanoparticles, are a recently reported effective way to loosen up the biofilm structure in order to enhance drug transport and efficacy. In the present study, we explored if the disruptive force of VNB can be used simultaneously to interfere with the biofilm structure and trigger antibiotic release from light-responsive nanocarriers. The antibiotic tobramycin was incorporated in two types of light-responsive nanocarriers—liposomes functionalized with gold nanoparticles (Lip-AuNP) and graphene quantum dots (GQD)—and their efficacy was evaluated on Pseudomonas aeruginosa biofilms. Even though the anti-biofilm efficacy of tobramycin was improved by liposomal encapsulation, electrostatic functionalization with 70 nm AuNP unfortunately resulted in premature leakage of tobramycin in a matter of hours. Laser-irradiation consequently did not further improve P. aeruginosa biofilm eradication. Adsorption of tobramycin to GQD, on the other hand, did result in a stable formulation with high encapsulation efficiency, without burst release of tobramycin from the nanocarriers. However, even though laser-induced VNB formation from GQD resulted in biofilm disruption, an enhanced anti-biofilm effect was not achieved due to tobramycin not being efficiently released from GQD. Even though this study was unsuccessful in designing suitable nanocarriers for simultaneous biofilm disruption and light-triggered release of tobramycin, it provides insights into the difficulties and challenges that need to be considered for future developments in this regard.

Necrosis is associated with a profound inflammatory response. The regulation of necrosis-associated inflammation, particularly the mechanisms responsible for resolution of inflammation are incompletely characterized. Nanoparticles are known to induce plasma membrane damage and necrosis followed by sterile inflammation. We observed that injection of metabolically inert nanodiamonds resulted in paw edema in WT and Ncf1** mice. However, while inflammation quickly resolved in WT mice, it persisted over several weeks in Ncf1** mice indicating failure of resolution of inflammation. Mechanistically, NOX2-dependent reactive oxygen species (ROS) production and formation of neutrophil extracellular traps (NETs) were essential for the resolution of necrosis-induced inflammation: Hence, by evaluating the fate of the particles at the site of inflammation, we observed that Ncf1** mice deficient in NADPH-dependent ROS failed to generate granulation tissue therefore being unable to trap the nanodiamonds. These data suggest that NOX2-dependent NETosis is crucial for preventing the chronification of the inflammatory response to tissue necrosis by forming NETosis-dependent barriers between the necrotic and healthy surrounding tissue.

The article reports on the strong linking of dopamine derivatives as a simple and a versatile strategy for the surface functionalization of hydroxyl-terminated nanodiamond (ND–OH) particles. Azide- (ND–N3) or poly-N-isopropylacrylamide-terminated (ND–PNIPAM) particles were obtained from ND–OH particles through the reaction with the corresponding dopamine derivatives. The azide-terminated ND particles were further derivatized with a fluorescent probe, alkynyl-pyrene, via copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. The modified ND particles were characterized using transmission Fourier transform infrared (FTIR) spectroscopy, UV–vis spectroscopy, electrochemical measurements, thermogravimetric analysis (TGA), and particle size measurements. The surface loading of ND particles with dopamine was estimated from TGA and UV–vis spectroscopy and was found to be around 0.27 mmol g–1. Because of its simple, gentle nature and versatility, the chemistry developed in this work can be used as an avenue for the preparation of functional nanodiamond particles for various applications. [ABSTRACT FROM AUTHOR]