Scalable phosphorylated cellulose production with improved environmental sustainability, crosslinkability and processability using 3D bioprinting for dye remediation.

In the present work, phosphorylated cellulose (PC) gel has been produced following an environmentally benign approach using agro-based chemicals with improved yield. The PC gels produced were transparent, negatively charged with high consistency, charge content (1133.33 mmol/kg), degree of substitution (DS) of 0.183 and increased yield (>87 %). The XPS and EDS analysis confirms the covalently bonded phosphate groups at weight percent of 9.42 % and 11.01 %, respectively. The life cycle assessment (LCA) shows that PC gel production via the phosphorylation route is an ecologically favourable strategy compared with traditional TEMPO oxidation, resulting in 1.67 times lower CO2 emission. The rheological studies of PC gels show shear-thinning behaviour with improved 3D printability followed by heat-induced crosslinking of phosphate groups. The mechanistic insights for the condensation of phosphate to form a phosphoric ester group during cross-linking were evaluated through 31P solid-state NMR and XPS studies. Interestingly, the 3D-printed structures showed high structural stability under both compression and tensile load in both dry and wet conditions, with high water absorption (5408.33 %) and swelling capacity of 700 %. The structures show improved methylene blue (MB) remediation capabilities with a maximum removal efficiency of 99 % for 10-200 mg/L and more than seven times reusability. This work provides a green, facile and energy-efficient strategy for fabricating PCs with easy processability through additive manufacturing techniques for producing value-added products, opening up new avenues for high-performance applications.

Biogenic synthesis of gold nanoparticles using dual extract of tulsi-Vinca for breast cancer tumor regression in mice.

Aim: This work aims to synthesize the gold nanoparticles (GNPs) using a dual extract of tulsi and Vinca (T+V-Gold) for breast cancer tumor regression. Methods: The GNPs were synthesized and characterized for their microscopic, spectroscopic and crystalline properties. Further, the GNPs were investigated for in vitro and in vivo studies for the treatment of the 4T1-induced triple-negative breast cancer murine model. Results: The GNPs for 4T1 tumor-challenged mice resulted in delayed tumor development and lower tumor burden, with T+V-Gold demonstrating the highest prevention of tumor spread. The antitumor effect of T+V-Gold is highly significant in the glutathione family antioxidants glutathione S-transferase and glutathione in tumor tissue samples. Conclusion: The bioefficacy and anticancer outcomes of T+V-Gold nanoformulation can be used as therapeutic agents and drug-delivery vehicles.

3D printable, injectable amyloid-based composite hydrogel of bovine serum albumin and aloe vera for rapid diabetic wound healing.

Protein-based biomaterials, particularly amyloids, have sparked considerable scientific interest in recent years due to their exceptional mechanical strength, excellent biocompatibility and bioactivity. In this work, we have synthesized a novel amyloid-based composite hydrogel consisting of bovine serum albumin (BSA) and aloe vera (AV) gel to utilize the medicinal properties of the AV gel and circumvent its mechanical frangibility. The synthesized composite hydrogel demonstrated an excellent porous structure, self-fluorescence, non-toxicity, and controlled rheological properties. Moreover, this hydrogel possesses inherent antioxidant and antibacterial properties, which accelerate the rapid healing of wounds. The in vitro wound healing capabilities of the synthesized composite hydrogel were evaluated using 3T3 fibroblast cells. Moreover, the efficacy of the hydrogel in accelerating chronic wound healing via collagen crosslinking was investigated through in vivo experiments using a diabetic mouse skin model. The findings indicate that the composite hydrogel, when applied, promotes wound healing by inducing collagen deposition and upregulating the expression of vascular endothelial growth factor (VEGF) and its receptors. We also demonstrate the feasibility of the 3D printing of the BSA-AV hydrogel, which can be tailored to treat various types of wound. The 3D printed hydrogel exhibits excellent shape fidelity and mechanical properties that can be utilized for personalized treatment and rapid chronic wound healing. Taken together, the BSA-AV hydrogel has great potential as a bio-ink in tissue engineering as a dermal substitute for customizable skin regeneration.

Effect of carbon quantum dots derived from extracts of UV-B-exposed Eclipta alba on alcohol-induced liver cirrhosis in Golden Hamster.

The Eclipta alba plant is considered hepatoprotective, owing to its phytoconstituents wedelolactone. In the current study, effect of elevated ultraviolet-B (eUV-B) radiation was investigated on biochemical, phytochemical, and antioxidative enzymatic activities of E. alba (Bhringraj) plant. The UV-B exposure resulted in an increase in oxidative stress, which has caused an imbalance in phytochemical, biochemical constituents, and induced antioxidative enzymatic activities. It was observed that the UV-B exposure promoted wedelolactone yield by 23.64%. Further, the leaf extract of UV-B-exposed plants was used for the synthesis of carbon quantum dots (CQDs) using low cost, one-step hydrothermal technique and its biocompatibility was studied using in vitro MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay on HepG2 liver cell line. It revealed no toxicity in any treatment groups in comparison to the control. Both CQDs and leaf extract were orally administered to the golden hamster suffering from alcohol-induced liver cirrhosis. In the morphometric study, it was clearly observed that a combination of UV-B-exposed leaf extract and synthesized CQDs delivered the best result with maximum recovery of liver tissues. The present study reveals the positive impact of UV-B exposure on the medicinally important plant, increased yield of wedelolactone, and its enhanced hepatoprotective efficacy for the treatment of damaged liver tissues.

Fabrication of white light emitting diodes via high yield surface passivated carbon quantum dots doped with terbium.

Exploiting the unique characteristics of various materials to create novel hybrid materials opens up innovative possibilities for cutting-edge applications across numerous fields. Here, we have synthesized novel surface functionalized photoluminescent carbon quantum dots (CQDs) doped with a rare-earth element (Tb3+) for white light emitting diodes. High quantum yield CQDs were produced utilizing Plumeria leaves as a precursor using a one-step hydrothermal approach, and further, its optical characterization was thoroughly investigated. Herein, the functionalized CQDs demonstrate excitation-independent electroluminescence performance. The UV-LED chip and functionalized CQD were combined to create a device that emits cold white light with Commission Internationale de L'Eclairage coordinates of (0.33, 0.34), a corresponding correlated color temperature of 4995 K and color rendering index of 84.2.

A Strategic Review on Carbon Quantum Dots for Cancer-Diagnostics and Treatment.

The understanding of the genesis of life-threatening cancer and its invasion calls for urgent development of novel technologies for real-time observations, early diagnosis, and treatment. Quantum dots (QDs) grabbed the spotlight in oncology owing to their excellent photostability, bright fluorescence, high biocompatibility, good electrical and chemical stability with minimum invasiveness. Recently, carbon QDs (CQDs) have become popular over toxic inorganic QDs in the area of bioimaging, biosensing, and drug delivery. Further, CQDs derived from natural sources like biomolecules and medicinal plants have drawn attention because of their one-pot, low-cost and ease of synthesis, along with remarkable tunable optical properties and biocompatibility. This review introduces the synthesis and properties of CQDs derived from natural sources, focusing on the applicability of CQD-based technologies as nano-theranostics for the diagnosis and treatment of cancer. Furthermore, the current issues and future directions for the transformation of CQDs-based nanotechnologies to clinical applications are highlighted.

Large Area Few-Layer Hexagonal Boron Nitride as a Raman Enhancement Material.

Increasingly, two-dimensional (2D) materials are being investigated for their potential use as surface-enhanced Raman spectroscopy (SERS) active substrates. Hexagonal Boron Nitride (hBN), a layered 2D material analogous to graphene, is mostly used as a passivation layer/dielectric substrate for nanoelectronics application. We have investigated the SERS activity of few-layer hBN film synthesized on copper foil using atmospheric pressure chemical vapor deposition. We have drop casted the probe molecules onto the hBN substrate and measured the enhancement effect due to the substrate using a 532 nm excitation laser. We observed an enhancement of ≈103 for malachite green and ≈104 for methylene blue and rhodamine 6G dyes, respectively. The observed enhancement factors are consistent with the theoretically calculated interaction energies of MB > R6G > MG with a single layer of hBN. We also observed that the enhancement is independent of the film thickness and surface morphology. We demonstrate that the hBN films are highly stable, and even for older hBN films prepared 7 months earlier, we were able to achieve similar enhancements when compared to freshly prepared films. Our detailed results and analyses demonstrate the versatility and durability of hBN films for SERS applications.

Color removal from model dye effluent using PVA-GA hydrogel beads.

A low cost polyvinyl alcohol-glutaraldehyde cross-linked hydrogel beads were prepared and used for color removal from model industrial effluent containing Congo Red dye, using adsorption technique. The adsorption studies were performed using batch and fixed-bed reactor. Developed adsorbent, achieved adsorption capacity as high as ~34 mg of dye per gram of bead (condition: pH 6 and 45 °C). These beads were re-used for 7 times (many more runs possible) to remove the color from model dye effluent, without much loss in removal efficiency. Batch studies revealed a multi-layer adsorption governed by Harkins Jura model. Whereas the adsorption kinetics followed fractal like pseudo second order model, controlled by intraparticle diffusion phenomena. The fixed bed studies revealed steeper break through curves during adsorption operation when high dye influent rates and low bed height were used. This behaviour by the fixed bed reactor was best explained by the Thomas mathematical model. Studies further demonstrated that an external and internal mass diffusion become no more rate limiting during these experiments.

Printability assessment of psyllium husk (isabgol)/gelatin blends using rheological and mechanical properties.

The primary goal of this study is to highlight the rheological and mechanical properties of a new blend composed of naturally-derived hydrogel materials- psyllium husk (PH) and gelatin (G) for its potential use in three-dimensional (3D) printing technology. The mixtures were prepared at various weight ratios of 100PH, 75PH + 25G and 50PH + 50G. A suitable selection of the printable ink was made based on the preliminary screening steps of manual filament drop test and layer stacking by 3D printing. Printing of the common features such as hexagon and square grids helped evaluating shape fidelity of the chosen ink. Although 50PH + 50G blend was found meeting most of the criteria for an ideal 3D printable ink, rheological and mechanical characterizations have been performed for all the ratios of polymeric blends. This study documents the correlation between various factors of rheology that should be taken into account while categorizing any biomaterial as a printable ink. Yield stress was measured as 18.59 ± 4.21 Pa, 268.74 ± 13.56 Pa and 109.16 ± 9.85 Pa for 50PH + 50G, 75PH + 25G and 100PH, respectively. Similarly, consistency index (K) and flow index (n) were calculated using the power law equation and found as 49.303 ± 4.17, 530.59 ± 10.92, 291.82 ± 10.53 and 0.275 ± 0.04, 0.05 ± 0.005, 0.284 ± 0.04 for 50PH + 50G, 75PH + 25G and 100PH, respectively. The loss modulus (G″) was observed dominating over storage modulus (G') for 50PH + 50G, that depicts its liquid-like property; whereas storage modulus (G') was found dominating in case of 75PH + 25G and 100PH, indicating their solid-like characteristics. In addition, the loss tangent value (tan δ) of 50PH + 50G was observed exceeding unity (1.05), supporting its plastic behavior, unlike 75PH + 25G (0.5) and 100PH (0.33) whose loss tangent values were estimated less than unity revealing their elastic behavior. Also, 50PH + 50G was found to have the highest mechanical strength amongst the three blends with a Young's modulus of 9.170 ± 0.0881 kPa.

Synthesis and characterization of novel protein nanodots as drug delivery carriers with an enhanced biological efficacy of melatonin in breast cancer cells.

Melatonin is a potent antioxidant, chemotherapeutic and chemo preventive agent against breast cancer. However, its short half-life is one of the major limitations in its application as a therapeutic drug. To overcome this issue, the green-emitting protein nanodot (PND) was synthesized by a one-step hydrothermal method for loading melatonin. The synthesized pH-7 and pH-2 PND showed a quantum yield of 22.1% and 14.0%, respectively. The physicochemical characterization of both PNDs showed similar morphological and functional activities. Furthermore, the biological efficacy of melatonin-loaded PND (MPND) was evaluated in a breast cancer cell line (MDA-MB-231) for live-cell imaging and enhanced nano-drug delivery efficacy. Interestingly, the permeability of neutral pH PND in both cell cytoplasm and nucleus nullifies the limitations of real-time live-cell imaging, and ensures nuclear drug delivery efficacy. Neutral pH PND showed better cell viability and cytotoxicity as a fluorescence bioimaging probe compared to acidic PND. The bioavailability and cell cytotoxicity effect of MPND on MDA-MB-231 breast cancer cells were studied through confocal and migration assay. Results showed that MPND causes enhanced bioavailability, better cellular uptake, and inhibition of the migration of breast cancer cells as compared to the drug alone. Besides, the synthesized MPND showed no sign of fluorescence quenching even at a high concentration of melatonin, making it an ideal nanocarrier for bioimaging and drug delivery.

Water-Templated, Polysaccharide-rich Bioartificial 3D Microarchitectures as Extra-Cellular Matrix Bioautomatons.

This is the first report of exploiting the "quasi-spherical" shape of water molecules for recapitulating a true human extracellular matrix (ECM). Herein, water behaved as a quasi-spherical porogen, for engineering polysaccharide-rich and chemically defined 3D-microarchitecture, with semi-interpenetrating networks (S-IPNs). Furthermore, their viscoelastic behavior along with a heterogeneous, fibroporous morphology, facilitated instructive, self-remodeling of the bioartificial scaffolds, thence effectively permitting and promoting the growth of 3D tumor spheroids of divergent origins. The hybrid composites displayed reproducible, uniform tumor spheroids with a Z-depth of ∼65 ± 2 µm in case of human adenocarcinoma (DLD-1) and ∼54 ± 3 µm for human glioblastoma cells (U-251) (vs. nonuniform spheroids, on Agarose matrix). Thereafter, their capacity for anticancer drug screening was examined using limited cancer drugs. The conflicting drug screening results for Etoposide's reduced efficacy on glioblastoma cells cultured on our 3D matrix could be ascribed to decreased drug access and thus lower ingression. Nonetheless, adenocarcinoma's resistance to Camptothecin was paralleled. Moreover, their potential for real-time, high-content, phenotypic precision oncology was affirmed by the exceptional transparency of the synthesized composite. Since this 3D microarchitecture typifies ECM bioautomaton, this matrix can also be wielded for precision oncology.

DNA biodots based targeted theranostic nanomedicine for the imaging and treatment of non-small cell lung cancer.

The light absorption and emission characteristics of DNA biodots (DNA-BD), along with biocompatibility, give them a high potential for use in various medical applications, particularly in diagnostic purpose. DNA, under high pressure and temperature, condenses to form luminescent biodots. The objective of this research is to develop DNA-biodots (BD) loaded and cetuximab conjugated targeted theranostic liposomes of etoposide for lung cancer imaging and therapy. Theranostic liposomes were prepared by using the solvent injection method and characterized for their particle size, polydispersity, zeta potential, encapsulation efficiency, and pH-dependent in-vitro release, SEM, TEM AFM, EDX, and XRD. The t50% (time at which 50% of the drug releases from the preparation) of the formulations was pH-dependent, with a significant increase in the release at lower pH (5.5). To kill A549 adenocarcinoma cells, the etoposide (control) required significantly (p < 0.05) higher drug concentrations in comparison to non-targeted and; the non-targeted formulation required more concentrations in comparison to targeted liposomes. The in-vivo results demonstrated that CTX-TPGS decorated theranostic liposomes could be a promising carrier for lung theranostics due to their nano-size and selectivity towards EGFR overexpressed cells which provided an improved NSCLC targeted delivery of ETP in comparison to the non-targeted and control formulations.

Sandalwood-derived carbon quantum dots as bioimaging tools to investigate the toxicological effects of malachite green in model organisms.

Malachite green is an N-methylated diaminophenylmethane dye that has generated much concern over its suggestive carcinogenic nature. After its excessive use in aquaculture industry as an effective ectoparasitide, much debate was raised over its toxicological effects leading to scientific studies conducted on animal models. Even after several bans, malachite green is still easily available in many parts of the world and unscrupulously even used to give green vegetables a fresher look. This study aims to address this concern by systematically studying the toxicological effects of malachite green through bioimaging in plant and animal cell and tissue. Sandalwood-derived carbon quantum dots have been used as a bioimaging tool since they are non-cytotoxic and show excellent fluorescence properties. Onion tissues demonstrate the translocation of the dye inside cells having high affinity for the nuclei and cell walls. Toxicological effects on the growth of Vigna radiata (mung beans) have been studied methodically. Bioimaging of the transverse cross-section of the dye-treated plant root shows a significant difference from the control. In animal cells, dose-dependent decrease in cell viability of MG-63 cells was observed with MG. CQD showed good fluorescence in both cytoplasm and nucleus of MG63 cells. In addition, CQDs were employed as a great tool for bioimaging of the histopathologically adverse effects of MG in Golden hamster animal model. This study showed CQDs could be used as an alternative non-site specific fluorescent probe for cell and tissue imaging for better visualization of cell and tissue architectural changes.

Characterization of Self-Assembled Protein Scaffolds from Collagen-Mimetic Peptides.

Collagen-mimetic peptides have been utilized to form structures of different morphology for various biomedical and nanotechnology applications. This chapter describes the characterization of collagen-mimetic peptide self-assembled structures formed by tuning the interactions between peptides. Inclusion of varying hydrophobicity, electrostatic forces, and stereoselectivity was mainly employed in CMP designs discussed herein. The role of these forces can be assessed using multiple characterization techniques. Light scattering techniques have been employed to study the aggregation kinetics of self-assembled nanostructures and to investigate the net charge distribution of peptides. Spectroscopy techniques like circular dichroism, fluorescence, and absorption spectroscopy have been utilized to decipher the secondary structures of peptide and binding of the peptides with dyes. Imaging techniques helped in resolving the morphology of the self-assembled structures. Confocal fluorescence microscopy and differential scanning calorimetry helped in indirect assessment of hydrophobicity and X-ray studies to determine the inter-helical spacing between the triple helical peptides of the higher order structures.