Presently, nanocarriers (NCs) have gained huge attention for their structural ability, good biocompatibility, and biodegradability. The development of effective NCs with stimuli-responsive properties has acquired a huge interest among scientists. When developing drug delivery NCs, the fundamental goal is to tackle the delivery-related problems associated with standard chemotherapy and to carry medicines to the intended sites of action while avoiding undesirable side effects. These nanocarriers were able of delivering drugs to tumors through regulating their pH, temperature, enzyme responsiveness. With the use of nanocarriers, chemotherapeutic drugs could be supplied to tumors more accurately that can equally encapsulate and deliver them. Material carriers for chemotherapeutic medicines are discussed in this review keeping in viewpoint of the structural properties and targeting methods that make these carriers more therapeutically effective, in addition to metabolic pathways triggered by drug-loaded NCs. Largely, the development of NCs countering to endogenous and exogenous stimuli in tumor regions and understanding of mechanisms would encourage the progress for tumor therapy and precision diagnosis in future. Graphical Abstract
Cold-active enzymes increase their catalytic efficiency at low-temperature, introducing structural flexibility at or near the active sites. Inevitably, this feat seems to be accompanied by lower thermal stability. These characteristics have made cold-active enzymes into attractive targets for the industrial applications, since they could reduce the energy cost in the reaction, attenuate side-reactions, and simply be inactivated. In addition, the increased structural flexibility could result in broad substrate specificity for various non-native substrates, which is called substrate promiscuity. In this perspective, we deal with a less addressed aspect of cold-active enzymes, substrate promiscuity, which has enormous potential for semi-synthesis or enzymatic modification of fine chemicals and drugs. Further structural and directed-evolutional studies on substrate promiscuity of cold-active enzymes will provide a new workhorse in white biotechnology.
In this study, we synthesized the cobalt(II) chelation free complexes (1–3) with the general formula of [CoCl2L2] containing monodentate ligands (L=2‐methylbenzimidazole (L1), 2‐methylbenzoxazole (L2), and 2‐methylbenzothiazole (L3) and fully characterized by UV‐vis, FT‐IR spectroscopy, and the crystal structures of 1–3 were determined by X‐ray crystallography. Complexes 1–3 showed substantial antibacterial activity against tested bacteria. Complexes 2 and 3 were more active against S. aureus with the Minimum Inhibitory concentration (MIC) value of 12.5 μg/mL compared to other bacteria. Complexes 1–3 exhibited strong synergy with ampicillin (AMP) against Methicillin Resistant S. aureus strains (MRSA). Interestingly, complexes 2 and 3 in combination with AMP showed the membrane permeabilization of MRSA. This indicates that complexes 2 and 3 in combination with AMP had bacterial membrane disruption as a possible mechanism of action.
Liver-expressed antimicrobial peptides (LEAPs) are cysteine-containing cationic peptides. LEAP-1 and LEAP-2 are eight- and four-cysteine containing antimicrobial peptides found in animals, respectively. LEAP-1 is widely known as antibacterial peptide involved in the innate immunity of fish, but the roles of LEAP-1 and LEAP-2 in Antarctic fish species are unknown. In the present study, we synthesized and characterized novel LEAPs with four and eight cysteine residues, derived from Antarctic notothenioid (Dissostichus mawsoni) and Antarctic eelpout (Lycodichthys dearborni). Circular dichroism spectroscopy of these peptides showed a typical β-sheet conformation. The LEAPs were found to be bactericidal against gram-positive as well as gram-negative bacteria. In the SYTOX green uptake assay, LEAPs did not trigger any significant increase in fluorescence. However, LEAPs competitively bound to DNA and replaced the ethidium bromide (EB) dye. To determine the effect of temperature on the activity of LEAPs, we evaluated the antibacterial activity against Listeria monocytogenes at 5, 15, 25, and 35 °C. The results showed that the antibacterial activity of LEAPs increased with a decrease in temperature, which may indicate that the Antarctic fish LEAP are evolutionarily adapted. Taken together, our results suggest that novel Antarctic LEAPs are bactericidal peptides with the likely mode of action being DNA binding and may be evolved to adapt to cold temperature.
In this study, we attempted to synthesize visible light active nano-sized photocatalysts using metal oxides such as zinc oxide, zirconium oxide, tungsten oxide, and strontium titanium oxide with (MoCl5)2 as a dopant by the simple ball-milling method. Fourier-transform infrared spectroscopy data confirmed the presence of M-O-Mo linkage (M = Zn, Zr, W, and SrTi) in all the molybdenum-doped metal oxides (MoMOs), but only MoZnO inhibited the growth of the bloom-forming Microcystis aeruginosa under visible light in a concentration-dependent manner up to 10 mg/L. Further, structural characterization of MoZnO using FESEM and XRD exhibited the formation of typical hexagonal wurtzite nanocrystals of approximately 4 nm. Hydroxyl radical (·OH), reactive oxygen species (ROS), and lipid peroxidation assays revealed ·OH generated by MoZnO under the visible light seemed to cause peroxidation of the lipid membrane of M. aeruginosa, which led to an upsurge of intracellular ROS and consequently introduced the agglomeration of cyanobacteria. These results demonstrated that nano-sized MoZnO photocatalyst can be easily synthesized in a cost-effective ball-mill method and utilized for biological applications such as the reduction of harmful algal blooms. Further, our study implies that a simple ball-milling method can provide an easy, green, and scalable route for the synthesis of visible light active doped metal oxides.
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