Neuromodulation by nanozymes and ultrasound during Alzheimer's disease management.

Alzheimer's disease (AD) is a neurodegenerative disorder with complex pathogenesis and effective clinical treatment strategies for this disease remain elusive. Interestingly, nanomedicines are under extensive investigation for AD management. Currently, existing redox molecules show highly bioactive property but suffer from instability and high production costs, limiting clinical application for neurological diseases. Compared with natural enzymes, artificial enzymes show high stability, long-lasting catalytic activity, and versatile enzyme-like properties. Further, the selectivity and performance of artificial enzymes can be modulated for neuroinflammation treatments through external stimuli. In this review, we focus on the latest developments of metal, metal oxide, carbon-based and polymer based nanozymes and their catalytic mechanisms. Recent developments in nanozymes for diagnosing and treating AD are emphasized, especially focusing on their potential to regulate pathogenic factors and target sites. Various applications of nanozymes with different stimuli-responsive features were discussed, particularly focusing on nanozymes for treating oxidative stress-related neurological diseases. Noninvasiveness and focused application to deep body regions makes ultrasound (US) an attractive trigger mechanism for nanomedicine. Since a complete cure for AD remains distant, this review outlines the potential of US responsive nanozymes to develop future therapeutic approaches for this chronic neurodegenerative disease and its emergence in AD management.

Self-Signal-Triggered Drug Delivery System for Tumor Therapy Using Cancer Cell Membrane-Coated Biocompatible Mn3O4 Nanocomposites.

In anti-cancer metastasis treatment, precise drug delivery to cancer cells remains a challenge. Innovative nanocomposites are developed to tackle these issues effectively. The approach involves the creation of manganese oxide (Mn3O4) nanoparticles (NPs) and their functionalization using trisodium citrate to yield functionalized Mn3O4 NPs (F-Mn3O4 NPs), with enhanced water solubility, stability, and biocompatibility. Subsequently, the chemotherapeutic drug doxorubicin (DOX) is encapsulated with Mn3O4 NPs, resulting in DOX/Mn3O4 NPs. To achieve cell-specific targeting, These NPs are coated with HeLa cell membranes (HCM), forming HCM/DOX/Mn3O4. For further refinement, a transferrin (Tf) receptor is integrated with cracked HCM to create Tf-HCM/DOX/Mn3O4 nanocomposites (NC) with specific cell membrane targeting capabilities. The resulting Tf-HCM/DOX/Mn3O4 NC exhibits excellent drug encapsulation efficiency (97.5%) and displays triggered drug release when exposed to NIR laser irradiation in the tumor's environment (pH 5.0 and 6.5). Furthermore, these nanocomposites show resistance to macrophage uptake and demonstrate homotypic cancer cell targeting specificity, even in the presence of other tumor cells. In vitro toxicity tests show that Tf-HCM/DOX/Mn3O4 NC achieves significant anticancer activity against HeLa and BT20 cancer cells, with percentages of 76.46% and 71.36%, respectively. These results indicate the potential of Tf-HCM/DOX/Mn3O4 NC as an effective nanoplatform for chemo-photothermal therapy.

Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application.

In this study, diselenide (Se-Se) and disulfide (S-S) redox-responsive core-cross-linked (CCL) micelles were synthesized using poly(ethylene oxide)2k-b-poly(furfuryl methacrylate)1.5k (PEO2k-b-PFMA1.5k), and their redox sensitivity was compared. A single electron transfer-living radical polymerization technique was used to prepare PEO2k-b-PFMA1.5k from FMA monomers and PEO2k-Br initiators. An anti-cancer drug, doxorubicin (DOX), was incorporated into PFMA hydrophobic parts of the polymeric micelles, which were then cross-linked with maleimide cross-linkers, 1,6-bis(maleimide) hexane, dithiobis(maleimido) ethane and diselenobis(maleimido) ethane via Diels-Alder reaction. Under physiological conditions, the structural stability of both S-S and Se-Se CCL micelles was maintained; however, treatments with 10 mM GSH induced redox-responsive de-cross-linking of S-S and Se-Se bonds. In contrast, the S-S bond was intact in the presence of 100 mM H2O2, while the Se-Se bond underwent de-crosslinking upon the treatment. DLS studies revealed that the size and PDI of (PEO2k-b-PFMA1.5k-Se)2 micelles varied more significantly in response to changes in the redox environment than (PEO2k-b-PFMA1.5k-S)2 micelles. In vitro release studies showed that the developed micelles had a lower drug release rate at pH 7.4, whereas a higher release was observed at pH 5.0 (tumor environment). The micelles were non-toxic against HEK-293 normal cells, which revealed that they could be safe for use. Nevertheless, DOX-loaded S-S/Se-Se CCL micelles exhibited potent cytotoxicity against BT-20 cancer cells. Based on these results, the (PEO2k-b-PFMA1.5k-Se)2 micelles can be more sensitive drug carriers than (PEO2k-b-PFMA1.5k-S)2 micelles.

Dual cross-linked chitosan/alginate hydrogels prepared by Nb-Tz 'click' reaction for pH responsive drug delivery.

A novel physically and chemically double-crosslinked hydrogel derived from chitosan oligosaccharide/alginate (COS/Alg) was developed by using norbornene (Nb)-tetrazine (Tz) click reaction for ketoprofen delivery. The properties of the hydrogel were evaluated by rheological, FTIR, TGA, XRD, SEM, swelling and drug release studies. The Nb-Tz chemical cross-linking facilitated outstanding hydrophobic drug loading (44% wt/wt of ketoprofen) and sustained release through a hydrophobic interaction mechanism between the drug and the used polysaccharides. The COS/Alg electrostatics network (10/10 of NH2/COOH molar ratio) generated the pH responsiveness, suppressing the release in simulated gastric fluid (below 10% for 2 h) and enhancing the release in simulated intestinal fluids (up to 84% for 24 h). The prepared hydrogel was non-toxic to human HEK-293 cells (95% cell viability). This work opens up a potential approach for preparing hydrophilic hydrogels from natural polysaccharides that can be used in the delivery of hydrophobic drugs.

Chitosan overlaid Fe3O4/rGO nanocomposite for targeted drug delivery, imaging, and biomedical applications.

A hybrid and straightforward nanosystem that can be used simultaneously for cancer-targeted fluorescence imaging and targeted drug delivery in vitro was reported in this study. A chitosan (CS) polymer coated with reduced graphene oxide (rGO) and implanted with Fe3O4 nanoparticles was fabricated. The fundamental physicochemical properties were confirmed via FT-IR, XRD, FE-SEM, HR-TEM, XPS, and VSM analysis. The in vivo toxicity study in zebrafish showed that the nanocomposite was not toxic. The in vitro drug loading amount was 0.448 mg/mL-1 for doxorubicin, an anticancer therapeutic, in the rGO/Fe3O4/CS nanocomposite. Furthermore, the pH-regulated release was observed using folic acid. Cellular uptake and multimodal imaging revealed the benefit of the folic acid-conjugated nanocomposite as a drug carrier, which remarkably improves the doxorubicin accumulation inside the cancer cells over-express folate receptors. The rGO/Fe3O4/CS nanocomposite showed enhanced antibiofilm and antioxidant properties compared to other materials. This study's outcomes support the use of the nanocomposite in targeted chemotherapy and the potential applications in the polymer, cosmetic, biomedical, and food industries.

Biocompatible properties of nano-drug carriers using TiO2-Au embedded on multiwall carbon nanotubes for targeted drug delivery.

Nanomaterial-based drug carriers have become a hot spot of research at the interface of nanotechnology and biomedicine because they allow efficient loading, targeted delivery, controlled release of drugs, and therefore are promising for biomedical applications. The current study made an attempt to decorate the multiwalled carbon nanotubes (MWCNT) with titanium dioxide­gold nanoparticles in order to enhance the biocompatibility for doxorubicin (DOX) delivery. The successful synthesis of nano drug carrier (NDC) was confirmed by XRD, XPS and UV-Visible spectroscopy. FESEM and TEM revealed that the morphology of NDC can be controlled by manipulating the reaction duration, MWCNT concentration and TiO2-Au source concentration. Results showed that TiO2 and Au nanoparticles were well coated on MWCNT. NDC had finely tuned biocompatible properties, as elucidated by hemolytic and antimicrobial assays. NDC also showed a high antioxidant potential, 80.7% expressed as ascorbic acid equivalents. Commercial DOX drug was utilized to treat A549 and MCF7 cancer cell lines showing improved efficiency by formulating it with NDC, which selectively delivered at the pH 5.5 with drug loading capacity of 0.45 mg/mL. The drug releasing capacity achieved by NDC was 90.66% for 10 h, a performance that far encompasses a wide number of current literature reports.

Synthesis and characterization of MWCNT/TiO2/Au nanocomposite for photocatalytic and antimicrobial activity.

A novel combination of titanium oxide (TiO2)/gold (Au)/multiwalled carbon nanotubes (MWCNTs) nanocomposite (NC) was synthesised by sol- gel method. MWCNT functionalisation by modified Hummers method. TiO2/Au nanoparticles (NPs) were synthesised by biological method using Terminalia chebula bark extract. MWCNT/TiO2/Au NC samples were characterised by X-ray diffraction, ultraviolet-visible-diffuse reflectance spectra, microRaman, scanning electron microscopy and high-resolution-transmission electron microscopy analyses. The photocatalytic performance of the obtained for NC toward the decomposition of congo-red and the antimicrobial activity for inhibition of Gram positive (Bacillus subtilis, Streptococcus pneumonia and Staphylococcus aureus), Gram negative (Shigella dysenderiae, Proteus vulgaris and Klebsiella pneumonia) and fungal strains have been evaluated and the results are compared with positive control ampicillin. The metal and metal-oxide NPs have a lower sorption capacity. The herbicidal bond to the tested CNTs by the combination of electron donor-acceptor interactions and hydrogen bonds. In particular, the dispersion of NC and control of sodium borohydride, it has more efficient effect on the photodegradation and antibacterial activity of positive control of ampicillin. The NC material has exhibited maximum photodegradation and antibacterial activity results of zone of inhibition when compared with control samples.

Guazuma ulmifolia bark-synthesized Ag, Au and Ag/Au alloy nanoparticles: Photocatalytic potential, DNA/protein interactions, anticancer activity and toxicity against 14 species of microbial pathogens.

In the present study, we focused on a quick and green method to fabricate Ag, Au and Ag/Au alloy nanoparticles (NPs) using the bark extract of Guazuma ulmifolia L. Green synthesized metal NPs were characterized using different techniques, including UV-Vis spectroscopy, FT-IR, XRD, AFM and HR-TEM analyses. The production of Ag, Au and Ag/Au alloy NPs was observed monitoring color change from colorless to brown, followed by pink and dark brown, as confirmed by UV-Vis spectroscopy characteristic peaks at 436, 522 and 510nm, respectively. TEM shed light on the spherical shapes of NPs with size ranges of 10-15, 20-25 and 10-20nm. Biosynthesized NPs showed good catalytic activity reducing two organic dyes, 4-nitrophenol (4-NP) and Congo red (CR). UV-vis spectroscopy, fluorescence, circular dichroism spectroscopy and viscosity analyses were used to investigate the NP binding with calf thymus DNA. The binding constant of NPs with DNA calculated in UV-Vis absorption studies were 1.18×104, 1.83×104 and 2.91×104M-1, respectively, indicating that NPs were able to bind DNA with variable binding affinity: Ag/Au alloy NPs>Ag NPs>Au NPs. Ag/Au alloy NPs also showed binding activity to bovine serum albumin (BSA) over the other NPs. Ag and Ag/Au alloy NPs exhibited good antimicrobial activity on 14 species of microbial pathogens. In addition, the cytotoxic effects of Ag/Au alloy NPs were studied on human cervical cancer cells (HeLa) using MTT assay. Overall, our work showed the promising potential of bark-synthesized Ag and Ag/Au alloy NPs as cheap sources to develop novel and safer photocatalytic, antimicrobial and anticancer agents.

Synthesis of cerium oxide nanoparticles using Gloriosa superba L. leaf extract and their structural, optical and antibacterial properties.

CeO2 nanoparticles (NPs) were green synthesized using Gloriosa superba L. leaf extract. The synthesized nanoparticles retained the cubic structure, which was confirmed by X-ray diffraction studies. The oxidation states of the elements (C (1s), O (1s) and Ce (3d)) were confirmed by XPS studies. TEM images showed that the NPs possessed spherical shape and particle size of 5nm. The Ce-O stretching bands were observed at 451cm(-1) and 457cm(-1) from the FT-IR and Raman spectra respectively. The band gap of the CeO2 NPs was estimated as 3.78eV from the UV-visible spectrum. From the photoluminescence measurements, the broad emission composed of eight different bands were found. The antibacterial studies performed against a set of bacterial strains showed that Gram positive (G+) bacteria were relatively more susceptible to the NPs than Gram negative (G-) bacteria. The toxicological behavior of CeO2 NPs was found due to the synthesized NPs with uneven ridges and oxygen defects in CeO2 NPs.