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To date, various nanodrug systems have been developed for different routes of administration, which include dendrimers, nanocrystals, emulsions, liposomes, solid lipid nanoparticles, micelles, and polymeric nanoparticles. Nanodrug systems have been employed to improve the efficacy, safety, physicochemical properties, and pharmacokinetic/pharmacodynamic profile of pharmaceutical substances. In particular, functionalized nanodrug systems can offer enhanced bioavailability of orally taken drugs, prolonged half-life of injected drugs (by reducing immunogenicity), and targeted delivery to specific tissues. Thus, nanodrug systems might lower the frequency of administration while providing maximized pharmacological effects and minimized systemic side effects, possibly leading to better therapeutic compliance and clinical outcomes. In spite of these attractive pharmacokinetic advantages, recent attention has been drawn to the toxic potential of nanodrugs since they often exhibit in vitro and in vivo cytotoxicity, oxidative stress, inflammation, and genotoxicity. A better understanding of the pharmacokinetic and safety characteristics of nanodrugs and the limitations of each delivery option is necessary for the further development of efficacious nanodrugs with high therapeutic potential and a wide safety margin. This review highlights the recent progress in nanodrug system development, with a focus on the pharmacokinetic advantages and safety challenges.

The objective of this study was to find one or more fungal strains that could be utilized to biosynthesize antifungal silver nanoparticles (AgNPs). Using morphological and molecular methods, Arthroderma fulvum was identified as the most effective fungal strain for synthesizing AgNPs. The UV-visible range showed a single peak at 420 nm, which corresponded to the surface plasmon absorbance of AgNPs. X-ray diffraction and transmission electron microscopy demonstrated that the biosynthesized AgNPs were crystalline in nature with an average diameter of 15.5±2.5 nm. Numerous factors could potentially affect the process of biosynthesis, and the main factors are discussed here. Optimization results showed that substrate concentration of 1.5 mM, alkaline pH, reaction temperature of 55°C, and reaction time of 10 hours were the optimum conditions for AgNP biosynthesis. Biosynthesized AgNPs showed considerable activity against the tested fungal strains, including Candida spp., Aspergillus spp., and Fusarium spp., especially Candida spp.

The increasing use of titanium dioxide nanoparticles (TiO NPs) across various fields has led to a growing concern regarding their environmental contamination and inevitable human exposure. Consequently, significant research efforts have been directed toward understanding the effects of TiO NPs on both humans and the environment. Notably, TiO NPs exposure has been associated with multiple impairments of the nervous system. This review aims to provide an overview of the documented neurotoxic effects of TiO NPs in different species and in vitro models. Following exposure, TiO NPs can reach the brain, although the specific mechanism and quantity of particles that cross the blood-brain barrier (BBB) remain unclear. Exposure to TiO NPs has been shown to induce oxidative stress, promote neuroinflammation, disrupt brain biochemistry, and ultimately impair neuronal function and structure. Subsequent neuronal damage may contribute to various behavioral disorders and play a significant role in the onset and progression of neurodevelopmental or neurodegenerative diseases. Moreover, the neurotoxic potential of TiO NPs can be influenced by various factors, including exposure characteristics and the physicochemical properties of the TiO NPs. However, a systematic comparison of the neurotoxic effects of TiO NPs with different characteristics under various exposure conditions is still lacking. Additionally, our understanding of the underlying neurotoxic mechanisms exerted by TiO NPs remains incomplete and fragmented. Given these knowledge gaps, it is imperative to further investigate the neurotoxic hazards and risks associated with exposure to TiO NPs.

Unmethylated cytosine-guanine dinucleotide-containing oligodeoxynucleotides (CpG ODNs), which are synthetic agonists of Toll-like receptor 9 (TLR9), activate humoral and cellular immunity and are being developed as vaccine adjuvants to prevent or treat cancers, infectious diseases, and allergies. Free CpG ODNs have been used in many clinical trials implemented to verify their effects. However, recent research has reported that self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes demonstrate higher adjuvant effects than free CpG ODNs, owing to their improved uptake efficiency into cells expressing TLR9. Moreover, protein/peptide-CpG ODN conjugates and nanomaterial-CpG ODN complexes are able to deliver CpG ODNs and antigens (or allergens) to the same types of cells, which enables a higher degree of prophylaxis or therapeutic effect. In this review, the author describes recent trends in the research and development of CpG ODN nanomedicines containing self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes, focusing mainly on the results of preclinical and clinical studies.

We previously found that ophthalmic formulations containing nanoparticles prepared by a bead mill method lead to an increase in bioavailability in comparison with traditional formulations (solution type). However, the transcorneal penetration pathway for ophthalmic formulations has not been explained yet. In this study, we investigated the mechanism of transcorneal penetration in the application of ophthalmic formulations containing indomethacin nanoparticles (IMC-NPs). IMC-NPs was prepared by the bead mill method. For the analysis of energy-dependent endocytosis, corneal epithelial (HCE-T) cell monolayers and removed rabbit cornea were thermoregulated at 4°C, where energy-dependent endocytosis is inhibited. In addition, for the analysis of different endocytosis pathways using pharmacological inhibitors, inhibitors of caveolae-mediated endocytosis (54 µM nystatin), clathrin-mediated endocytosis (40 µM dynasore), macropinocytosis (2 µM rottlerin) or phagocytosis (10 µM cytochalasin D) were used. The ophthalmic formulations containing 35-200 nm sized indomethacin nanoparticles were prepared by treatment with a bead mill, and no aggregation or degradation of indomethacin was observed in IMC-NPs. The transcorneal penetration of indomethacin was significantly decreased by the combination of nystatin, dynasore and rottlerin, and the decreased penetration levels were similar to those at 4°C in HCE-T cell monolayers and rabbit cornea. In the in vivo experiments using rabbits, dynasore and rottlerin tended to decrease the transcorneal penetration of indomethacin (area under the drug concentration - time curve in the aqueous humor [AUC ]), and the AUC in the nystatin-treated rabbit was significantly lower than that in non-treatment group. In addition, the AUC in rabbit corneas undergoing multi-treatment was obviously lower than that in rabbit corneas treated with each individual endocytosis inhibitor. We found that three energy-dependent endocytosis pathways (clathrin-dependent endocytosis, caveolae-dependent endocytosis and macropinocytosis) are related to the trans-corneal penetration of indomethacin nanoparticles. In particular, the caveolae-dependent endocytosis is strongly involved.

Indocyanine green (ICG), a near infrared (NIR) dye clinically approved in medical diagnostics, possesses great heat conversion efficiency, which renders itself as an effective photosensitizer for photothermal therapy (PTT) of cancer. However, there remain bottleneck challenges for use in PTT, which are the poor photo and plasma stability of ICG. To address these problems, in this research, ICG-loaded silver nanoparticles were prepared and evaluated for the applicability as an effective agent for photothermal cancer therapy. PEGylated bovine serum albumin (BSA)-coated silver core/shell nanoparticles were synthesized with a high loading of ICG (\"PEG-BSA-AgNP/ICG\"). Physical characterization was carried out using size analyzer, transmission electron microscopy, and Fourier transform infrared spectrophotometry to identify successful preparation and size stability. ICG-loading content and the photothermal conversion efficiency of the particles were confirmed with inductively coupled plasma mass spectrometry and laser instruments. In vitro studies showed that the PEG-BSA-AgNP/ICG could provide great photostability for ICG, and their applicability for PTT was verified from the cellular study results. Furthermore, when the PEG-BSA-AgNP/ICG were tested in vivo, study results exhibited that ICG could stably remain in the blood circulation for a markedly long period (plasma half-life: 112 min), and about 1.7% ID/g tissue could be accumulated in the tumor tissue at 4 h post-injection. Such nanoparticle accumulation in the tumor enabled tumor surface temperature to be risen to 50°C (required for photo-ablation) by laser irradiation and led to successful inhibition of tumor growth in the B16F10 s.c. syngeneic nude mice model, with minimal systemic toxicity. Our findings demonstrated that PEG-BSA-AgNPs could serve as effective carriers for delivering ICG to the tumor tissue with great stability and safety.

An attempt was made to control the surface charge of colloidal silica nanoparticles with 20 nm and 100 nm diameters. Untreated silica nanoparticles were determined to be highly negatively charged and have stable hydrodynamic sizes in a wide pH range. To change the surface to a positively charged form, various coating agents, such as amine containing molecules, multivalent metal cation, or amino acids, were used to treat the colloidal silica nanoparticles. Molecules with chelating amine sites were determined to have high affinity with the silica surface to make agglomerations or gel-like networks. Amino acid coatings resulted in relatively stable silica colloids with a modified surface charge. Three amino acid moiety coatings (L-serine, L-histidine, and L-arginine) exhibited surface charge modifying efficacy of L-histidine > L-arginine > L-serine and hydrodynamic size preservation efficacy of L-serine > L-arginine > L-histidine. The time dependent change in L-arginine coated colloidal silica was investigated by measuring the pattern of the backscattered light in a Turbiscan™. The results indicated that both the 20 nm and 100 nm L-arginine coated silica samples were fairly stable in terms of colloidal homogeneity, showing only slight coalescence and sedimentation.

The biological synthesis of nanoparticles (NPs) has become a new methodology for the eco-friendly production of NPs with high scalability and biocompatibility. Cyanobacteria are one of the most widespread microorganisms on Earth and have been proven to be successful biofactories for synthesizing NPs. It is challenging to discover new microalgae with the potential to synthesize NPs of small size with high stability.PurposeThe biological synthesis of nanoparticles (NPs) has become a new methodology for the eco-friendly production of NPs with high scalability and biocompatibility. Cyanobacteria are one of the most widespread microorganisms on Earth and have been proven to be successful biofactories for synthesizing NPs. It is challenging to discover new microalgae with the potential to synthesize NPs of small size with high stability.Nostoc muscorum Lukesova 2/91 was isolated, purified, and identified morphologically and genetically using microscopy and DNA sequencing. Volatile biomolecules in aqueous algal extracts were assessed using gas chromatography-mass spectroscopy (GC-MS).MethodsNostoc muscorum Lukesova 2/91 was isolated, purified, and identified morphologically and genetically using microscopy and DNA sequencing. Volatile biomolecules in aqueous algal extracts were assessed using gas chromatography-mass spectroscopy (GC-MS).Data showed that the main biomolecules were fatty acids and their esters, followed by secondary metabolites. Algal extract was used to convert silver nitrate (AgNO3) into silver NPs under various optimized parameters. 1 mM of AgNO3, 1:1 (V/V ratio of algal extract to AgNO3), 25 °C, under light illumination, for 24 h, at pH 7.4 were the optimum conditions for NP production (Nos@AgNPs). Nos@AgNPs were characterized using UV-VIS spectroscopy, FTIR, TEM, SEM, EDx, mapping, and a Zetasizer. The wavelength of Nos@AgNPs was 401.4 nm and their shapes were cubic to oval, with an average diameter of 11.8 ± 0.5 nm. FTIR spectroscopy revealed that proteins/polysaccharides could be the main reductants, whereas these molecules and/or fatty acids could be stabilizers for NP synthesis. Nos@AgNPs (86.15%) was silver and had a hydrodynamic diameter of 10.7 nm with a potential charge of -19.7 mV. Antiproliferative and antimicrobial activities of Nos@AgNPs were evaluated. Nos@AgNPs exhibited significant inhibitory activity against lung, colon, and breast cancer cells and considerable biocidal activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa.ResultsData showed that the main biomolecules were fatty acids and their esters, followed by secondary metabolites. Algal extract was used to convert silver nitrate (AgNO3) into silver NPs under various optimized parameters. 1 mM of AgNO3, 1:1 (V/V ratio of algal extract to AgNO3), 25 °C, under light illumination, for 24 h, at pH 7.4 were the optimum conditions for NP production (Nos@AgNPs). Nos@AgNPs were characterized using UV-VIS spectroscopy, FTIR, TEM, SEM, EDx, mapping, and a Zetasizer. The wavelength of Nos@AgNPs was 401.4 nm and their shapes were cubic to oval, with an average diameter of 11.8 ± 0.5 nm. FTIR spectroscopy revealed that proteins/polysaccharides could be the main reductants, whereas these molecules and/or fatty acids could be stabilizers for NP synthesis. Nos@AgNPs (86.15%) was silver and had a hydrodynamic diameter of 10.7 nm with a potential charge of -19.7 mV. Antiproliferative and antimicrobial activities of Nos@AgNPs were evaluated. Nos@AgNPs exhibited significant inhibitory activity against lung, colon, and breast cancer cells and considerable biocidal activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa.N. muscorum Lukesova 2/91 is an excellent source for the biofabrication of small and stable AgNPs with potent inhibitory effects against cancer and bacterial cells.ConclusionN. muscorum Lukesova 2/91 is an excellent source for the biofabrication of small and stable AgNPs with potent inhibitory effects against cancer and bacterial cells.

Photothermal therapy (PTT) is a therapeutic method in which photon energy is transformed into heat rapidly via different operations to extirpate cancer. Nanoparticles, such as carbon nanotubes (CNTs) have exceptional optical absorbance in visible and near infrared spectra. Therefore, they could be a good converter to induce hyperthermia in PTT technique. In our study, for improving the dispersibility of multiwalled CNTs in water, the CNTs were oxidized (O-CNTs) and then polyethylene glycol (PEG) was used for wrapping the surface of nanotubes. The formation of a thin layer of PEG around the nanotubes was confirmed through Fourier transform infrared, thermogravimetric analysis, and field emission scanning electron microscopy techniques. Results of thermogravimetric analysis showed that the amount of PEG component in the O-CNT-PEG was approximately 80% (w/w). Cell cytotoxicity study showed that O-CNT was less cytotoxic than pristine multiwalled nanotubes, and O-CNT-PEG had the lowest toxicity against HeLa and HepG2 cell lines. The effect of O-CNT-PEG in reduction of melanoma tumor size after PTT was evaluated. Cancerous mice were exposed to a continuous-wave near infrared laser diode (λ=808 nm, =2 W and =8 W/cm ) for 10 minutes once in the period of the treatment. The average size of tumor in mice receiving O-CNT-PEG decreased sharply in comparison with those that received laser therapy alone. Results of animal studies indicate that O-CNT-PEG is a powerful candidate for eradicating solid tumors in PTT technique.

Recent, outbreaks of new emergency zoonotic diseases have prompted an urgent need to develop fast, accurate, and portable screening assays for pathogen infections. Recombinase polymerase amplification (RPA) is sensitive and specific and can be conducted at a constant low temperature with a short response time, making it especially suitable for on-site screening and making it a powerful tool for preventing or controlling the spread of zoonoses. This review summarizes the design principles of RPA-based biosensors as well as various signal output or readout technologies involved in fluorescence detection, lateral flow assays, enzymatic catalytic reactions, spectroscopic techniques, electrochemical techniques, chemiluminescence, nanopore sequencing technologies, microfluidic digital RPA, and clustered regularly interspaced short palindromic repeats/CRISPR-associated systems. The current status and prospects of the application of RPA-based biosensors in zoonoses screening are highlighted. RPA-based biosensors demonstrate the advantages of rapid response, easy-to-read result output, and easy implementation for on-site detection, enabling development toward greater portability, automation, and miniaturization. Although there are still problems such as high cost with unstable signal output, RPA-based biosensors are increasingly becoming one of the most important means of on-site pathogen screening in complex samples involving environmental, water, food, animal, and human samples for controlling the spread of zoonotic diseases. Keywords: recombinase polymerase amplification, biosensor, zoonoses, rapid detection, nanomaterials