Potential Biomedical Applications Research Articles

Nanostructure properties and potential biomedical applications of Nelumbo nucifera Gaertn extracts

Nanostructure properties and potential biomedical applications of Nelumbo nucifera Gaertn extracts

An Oxygen‐Self‐Produced Nanoplatform Based on MnO2 for Relieving Hypoxia

AbstractManganese dioxide (MnO2) nanoparticles are increasingly recognized for their potential in biomedical applications, particularly in the realm of hypoxic cancer therapy, due to their unique physicochemical characteristics. This investigation introduces a novel, template‐free synthesis strategy. The reducing groups inherent in bovine serum albumin (BSA) facilitate a redox reaction with potassium permanganate (KMnO4), while the abundance of functional groups in BSA is instrumental in the formation of MnO2. The transmission electron microscopy (TEM) analysis has characterized the synthesized MnO2 nanoparticles, termed BM NPs, as spherical particles with a mean diameter of 210 nm and zeta potential of −40.1 mV measured by dynamic light scattering (DLS). The Fourier transform infrared (FT‐IR) spectrum of BM NPs exhibits the characteristic peak of MnO2 at 1113 cm−1 and 620 cm−1. Furthermore, the elemental composition of BM NPs has been ascertained through energy‐dispersive X‐ray (EDX) elemental mapping analysis. Though concentration of BM NPs up to 200 μg/mL, the survival rate of 4T1 cells remained approximately 75 %. Given that BM NPs at a concentration of 100 μg/mL significantly alleviate cellular hypoxia, the high oxygen‐generating capacity of these nanoparticles is proved, suggesting their suitability as a drug delivery system, especially in the context of hypoxic tumor microenvironments.

Antibacterial and Photocatalytic Applications of Silver Nanoparticles Synthesized from Lacticaseibacillus rhamnosus

The biosynthesis of silver nanoparticles (AgNPs) presents an innovative and sustainable approach in nanotechnology with promising applications in fields such as medicine, food safety, and pharmacology. In this study, AgNPs were successfully synthesized using the probiotic strain Lacticaseibacillus rhamnosus (BCRC16000), addressing challenges related to stability, biocompatibility, and scalability that are common in conventional nanoparticle production methods. The formation of AgNPs was indicated by a color change from yellow to brown, and UV–visible spectrophotometry confirmed their presence with a characteristic absorption peak at 443 nm. Furthermore, Fourier transform infrared (FTIR) spectroscopy revealed the involvement of biomolecules in reducing silver ions, which suggests their role in stabilizing the nanoparticles. In addition, field emission scanning electron microscopy (FE-SEM) showed significant morphological and structural changes. At the same time, dynamic light scattering (DLS) and zeta potential analyses provided valuable insights such as average size (199.7 nm), distribution, and stability, reporting a polydispersity index of 0.239 and a surface charge of −36.3 mV. Notably, the AgNPs demonstrated strong antibacterial activity and photocatalytic efficiency, underscoring their potential for environmental and biomedical applications. Therefore, this study highlights the effectiveness of Lacticaseibacillus rhamnosus in the biosynthesis of AgNPs, offering valuable antibacterial and photocatalytic properties with significant industrial and scientific implications.

Neutralizing VHH Antibodies Targeting the Spike Protein of PEDV

Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that infect pigs’ intestinal epithelial cells, causing high morbidity and mortality. Due to the rapid mutation of PEDV, vaccine efficacy is uncertain, prompting exploration of alternative treatments. Nanobodies, also known as variable heavy chain domains of heavy chain-only antibodies (VHHs), offer significant potential in biomedical applications due to their small size and high specificity. In this study, yeast two-hybrid technology was employed to screen for eight specific VHH sequences targeting the PEDV S protein from a synthetically constructed nanobody yeast library. The VHH genes were then cloned into expression plasmids for recombinant protein production, and the resulting VHHs (termed PEDV S-VHHs) were purified. Indirect immunofluorescence assay (IFA) and Western blotting analysis confirmed that these VHHs specifically bind to both PEDV and its S protein. Neutralization assays demonstrated that seven PEDV S-VHHs exhibited potent neutralizing activity against PEDV. Additionally, a combination of these seven antibodies showed enhanced antiviral effects. Preliminary predictions were also made regarding the binding sites between these VHHs and PEDV. The PEDV S-VHHs described in this study hold potential as candidates for the prevention and treatment of PEDV infection.

Activity-Based Dicyanoisophorone Derivatives: Fluorogenic Toolbox Enables Direct Visualization and Monitoring of Esterase Activity in Tumor Models.

The visualization and spatiotemporal monitoring of endogenous esterase activity are crucial for clinical diagnostics and treatment of liver diseases. Our research adopts a novel substrate hydrolysis-enzymatic activity (SHEA) approach using dicyanoisophorone-based fluorogenic ester substrates DCIP-R (R = R1-R6) to evaluate esterase preferences on diverse substrate libraries. Esterase-mediated hydrolysis yielded fluorescent DCIP-OH with a nanomolar detection limit in vitro. These probes effectively monitor ester hydrolysis kinetics with a turnover number of 4.73 s-1 and catalytic efficiency (kcat/Km) of 106 M-1 s-1 (DCIP-R1). Comparative studies utilizing two-photon imaging have indicated that substrates containing alkyl groups (DCIP-R1) as recognition elements exhibit enhanced enzymatic cleavage compared to those containing phenyl substitution on alkyl chains (DCIP-R4). Time-dependent variations in endogenous esterase levels were tracked in healthy and liver tumor models, especially in diethylnitrosamine (DEN)-induced tumors and HepG2-transplanted liver tumors. Overall, fluorescence signal quantifications demonstrated the excellent proficiency of DCIP-R1 in detecting esterase activity both in vitro and in vivo, showing promising potential for biomedical applications.

Mechanical enhancement of porous scaffolds through integration of auxetic and conventional structures

Additive manufacturing has revolutionized the fabrication of various porous structures using diverse biomaterials for preclinical and clinical applications. However, hybrid structures combining conventional and auxetic structures have been seldom explored, despite their immense potential for biomedical applications. This study aims to design various hybrid auxetic and conventional structures and demonstrate their mechanical properties using porous composite polycaprolactone/hydroxyapatite (PCL/HA) biomaterials. Our findings reveal that newly suggested structures can enhance Young’s modulus, yield stress, and energy absorption by up to 98.64%, 99.27%, and 98.61%, respectively, compared to the conventional structures. Moreover, all fabricated scaffolds exhibit porosity exceeding 90%, ensuring their suitability for tissue engineering applications.

Nanomedicine potential of Cymbopogon citratus Linn. –Biogenic synthesized silver nanoparticles: A study on antimicrobial and anticancer efficacy

Green synthesis methods for making nanoparticles using plant extracts have gained considerable attention in recent years, particularly because of their potential applications in nanomedicine. Plant biosynthesized nanoparticles have shown noteworthy biomedical uses in comparison. The silver nanoparticle (AgNP) synthesized using extracts from the leaves and flowers of Cymbopogon citratus Linn was investigated for its antibacterial and anticancer properties. The biosynthesized AgNPs were characterized using UV–Vis, FTIR, DLS, EDX and SEM. The presence of alcohol, alkene, and phytochemicals in the AgNPs was confirmed using FTIR analysis. The investigation using SEM with EDX spectroscopy confirmed that the AgNPs were both pure and in the form of nanocrystals. Furthermore, AgNPs demonstrated significant antibacterial activity by efficiently suppressing bacterial growth. The biosynthesized AgNPs exhibited a concentration-dependent reduction in the lung cancer-A549 cell growth. The ethanolic extracts of C. citratus flower-synthesized AgNPs contain a wide range of phytochemical constituents. These components have been shown to effectively modulate antibacterial and anticancer activities, superior tothe effects of leaf extracts synthesized AgNPs. Consequently, additional research is required to investigate the potential biomedical applications of these biosynthesized AgNPs.

Investigation of Elaeocarpus ganitrus seed (EGs) powder as a sustainable composite biomaterial: Effects of particle size on the mechanical, frictional, and thermal properties for potential biomedical applications

This study explores the potential of Elaeocarpus ganitrus seed (EGs) powder as a sustainable composite biomaterial, focusing on its particle size effects on the mechanical, frictional, and thermal properties of composite materials for potential biomedical applications such as prosthetics and implants. Composite specimens were produced using the compression hot molding method, utilizing EG powder particles of varying sizes (120, 140, and 200-mesh sieving). The influence of EG powder particle size on key properties was systematically investigated. The findings reveal that reducing the particle size of EGs leads to a decrease in density and hardness of the composite, with the largest particle size (BP1) resulting in the highest density and hardness. Friction coefficient measurements indicated suitability for biomedical applications where surface interaction and wear resistance are critical, such as joint prosthetics. Thermal analysis showed that BP1 exhibited superior thermal stability, with a maximum decomposition temperature (Tmax) exceeding 375 °C. Differential scanning calorimetry identified significant differences in glass transition temperature (Tg) and crystallization temperature (Tc) across specimens. The composites demonstrated exceptional thermal performance, surpassing previous benchmarks for biomaterials in high-temperature environments. The mechanical and thermal characteristics of Specimen BP1—2.725 g/cm3 density, 74 Shore D hardness, 0.159 coefficient of friction, 93.3% total residual, 378.14 °C Tmax, 426.25 °C Tc, and 376.87 °C Tg—suggest its potential for biomedical applications requiring durability and thermal resilience, such as in orthopedic devices and tissue engineering scaffolds.

Isolation, Characterization and Molecular Identification of Bacteria Associated with Green and Brown Seaweeds

Aims: The co-existence of bacterial communities along with macroalgae in marine environment develops a mutualistic relationship resulting in functional advantages for both the groups. The present research studied the composition of epiphytic bacteria associated with green (Ulva spp.) and brown seaweeds (Sargassum spp. and Padina spp.) sampled off Maharashtra coast, India, and their physiological and bioactive properties. Study Design: Green and brown seaweeds were collected from three locations along Maharashtra coast and analyzed for the associated bacteria. Place and Duration of Study: Seaweed samples analyzed in this study were from Kelwa, Manori and Ratnagiri along the Maharashtra coast. The analysis was performed during June to September 2021. Methodology: Bacteria from freshly collected seaweed samples were homogenized in saline, 10-fold serially diluted and plated on Zobell marine agar. Distinct colonies were selected and identified by a series of biochemical tests, followed by partial 16SrRNA gene sequencing. The physiological characteristics of the isolated bacteria were studied by screening for temperature and salinity tolerance, production of protease, lipase, agarose, amylase and biosurfactants. Results: The total seaweed bacterial count ranged from 4.5 ×103 to 2.9 × 104 CFU/g. Seventy-seven bacteria were isolated, 44 (57.14%) and 33 (42.85%) isolates from green and brown seaweeds respectively. The 16SrRNA sequencing of 20 representative isolates revealed the dominance of Bacillus spp., followed by Vibrio spp. Growth at 0°C was exhibited by all bacteria except Bacillus tequilensis, Bacillus altitudinis, Oceanobacillus iheyensis and one isolate of Vibrio spp. A majority of the isolates grew at 45°C. Vibrio spp. exhibited protease, amylase, gelatinase, and agarase activities, whereas the biosurfactant activity was commonly associated with Bacillus spp. Conclusion: The results of this study illustrate the occurrence of seaweed-associated beneficial bacteria exhibiting bioactive properties with potential biomedical applications.

Scalable Production and Biophysical Characterization of High-Molecular-Weight Relaxed and Tense Quaternary State Polymerized Human Hemoglobin as Potential Red Blood Cell Substitutes.

High-molecular-weight (HMW) (>500 kDa) glutaraldehyde-polymerized human hemoglobin (PolyhHb) is a promising hemoglobin-based oxygen carrier (HBOC) due to its decreased risk of vasoconstriction and oxidative tissue injury. Previously, HMW tense (T) quaternary state PolyhHb was synthesized at the pilot scale with tangential flow filtration (TFF) for the removal of low-molecular-weight species. However, T-state PolyhHb is limited to specific biomedical applications due to its low oxygen affinity, thus motivating the need to produce high oxygen affinity relaxed (R) quaternary state PolyhHb at the pilot scale. This study explored the pilot-scale synthesis and extensive biophysical characterization of both HMW T- and R-state PolyhHb. The resultant characterization demonstrated the successful synthesis of low and high oxygen affinity PolyhHb with increased molecular weight (∼1000-1500 kDa). Overall, T- and R-state PolyhHb provides a platform for manufacturing oxygen therapeutics with a diverse range of oxygen affinities and potential biomedical applications.

Collective buoyancy-driven dynamics in swarming enzymatic nanomotors

Enzymatic nanomotors harvest kinetic energy through the catalysis of chemical fuels. When a drop containing nanomotors is placed in a fuel-rich environment, they assemble into ordered groups and exhibit intriguing collective behaviour akin to the bioconvection of aerobic microorganismal suspensions. This collective behaviour presents numerous advantages compared to individual nanomotors, including expanded coverage and prolonged propulsion duration. However, the physical mechanisms underlying the collective motion have yet to be fully elucidated. Our study investigates the formation of enzymatic swarms using experimental analysis and computational modelling. We show that the directional movement of enzymatic nanomotor swarms is due to their solutal buoyancy. We investigate various factors that impact the movement of nanomotor swarms, such as particle concentration, fuel concentration, fuel viscosity, and vertical confinement. We examine the effects of these factors on swarm self-organization to gain a deeper understanding. In addition, the urease catalysis reaction produces ammonia and carbon dioxide, accelerating the directional movement of active swarms in urea compared with passive ones in the same conditions. The numerical analysis agrees with the experimental findings. Our findings are crucial for the potential biomedical applications of enzymatic nanomotor swarms, ranging from enhanced diffusion in bio-fluids and targeted delivery to cancer therapy.

Editorial for the Special Issue on Fundamentals and Applications of Micro/Nanorobotics

In recent years, microrobots have drawn extensive attention due to their promising potential in biomedical applications [...]

Nitric Oxide-Photodelivering Materials with Multiple Functionalities: From Rational Design to Therapeutic Applications.

The achievement of materials that are able to release therapeutic agents under the control of light stimuli to improve therapeutic efficacy is a significant challenge in health care. Nitric oxide (NO) is one of the most studied molecules in the fascinating realm of biomedical sciences, not only for its crucial role as a gaseous signaling molecule in the human body but also for its great potential as an unconventional therapeutic in a variety of diseases including cancer, bacterial and viral infections, and neurodegeneration. Handling difficulties due to its gaseous nature, reduced region of action due to its short half-life, and strict dependence of the biological effects on its concentration and generation site are critical questions to be solved for appropriate therapeutic uses of NO. Light-activatable NO precursors, namely, NO photodonors (NOPDs), address the above issues since they are stable in the dark and permit in a noninvasive fashion the remote-controlled delivery of NO on demand with great spatiotemporal precision. Engineering biocompatible materials with NOPDs and their combination with additional imaging, therapeutic, and phototherapeutic components leads to intriguing light-responsive multifunctional constructs exhibiting promising potential for biomedical applications. This contribution illustrates the most significant progress made over the last five years in achieving engineered materials including nanoparticles, gels, and thin films, sharing the common feature to deliver NO under the exclusive control of the biocompatible visible/near infrared light inputs. We will highlight the logical design behind the fabrication of these systems, illustrating the potential therapeutic applications with particular emphasis on cancer and bacterial infections.

The potential cutaneous benefits of bentonites and montmorillonites.

Bentonites and montmorillonites, natural clay minerals originating from volcanic ash, possess unique properties that have traditionally been utilized in industrial applications. Recently, their potential biomedical applications, particularly in dermatology, have garnered significant interest. This review explores the cutaneous benefits of bentonites and montmorillonites, highlighting their anti-inflammatory, wound-healing, oil-absorbing, drug delivery, photoprotective, and anti-aging effects. Evidence from in vitro experiments, animal studies, and preliminary clinical trials demonstrate that these clays can significantly reduce inflammation, accelerate wound healing, absorb excess oil, enhance drug delivery, protect against ultraviolet radiation, and improve skin hydration and elasticity. Larger scale randomized clinical trials (RCTs) are needed to further establish the safety and efficacy of bentonites and montmorillonites. Given the increasing consumer demand for natural ingredients in skincare, bentonites and montmorillonites present a promising area for further research and development in dermatologic applications.

Green synthesis of anethole-loaded zinc oxide nanoparticles enhances antibacterial strategies against pathogenic bacteria.

The threat of antibiotic resistance is escalating, diminishing the effectiveness of numerous antibiotics due to the rapid development of resistant bacteria. In response, the use of green-synthesized nanoparticle, alone or combined with antimicrobial agents, appears promising. This study explores the effectiveness of zinc oxide nanoparticles (ZnONPs) synthesized using Loranthus cordifolius leaf extracts and subsequently coated with anethole. The fabrication of these nanoparticles was confirmed via UV-Vis, FTIR and TEM analyses, ensuring the nanoparticles were produced as intended. Utilizing a nanoprecipitation process that excludes evaporation and drying, a high drug loading capacity of 16.59% was accomplished. The encapsulation efficiency for anethole was recorded at 88.23 ± 4.98%. Antibacterial efficacy was assessed by com paring the green-synthesized ZnONPs (average size: 14.47nm), anethole-loaded ZnONPs (average size: 14,75nm), and commercially sourced ZnONPs. The ZnONPs with anethole demonstrated superior inhibition against all tested bacterial strains, including Gram-negative species like Pseudomonas aeruginosa and Escherichia coli, and Gram-positive species like Bacillus subtilis and Staphylococcus aureus, outperforming the commercially available ZnONPs. Additionally, anethole-coated ZnONPs showed the greatest inhibition of Gyr-B activity (IC50 = 0.78 ± 0.2M), better than both green-synthesized and commercially available ZnONPs. These findings emphasize the enhanced antimicrobial properties of ZnONPs, particularly when combined with green synthesis and anethole loading, highlighting their potential in various biomedical applications.

A Diketopinic Reagent for the Reversible Bioconjugation to Arginine Residues on Native Antibodies.

Arginine is one of the less commonly targeted amino acids in protein bioconjugation, despite its unique reactivity and abundance on the surface of proteins. In this work, a molecule containing diketopinic acid and an azide handle was developed for the chemo-selective bioconjugation to arginine. This compound proved to be efficient for bioconjugation to IgG1 and IgG4 antibodies, achieving mono- and double-label conversion rates of 37-44 and 12-30%, respectively. Mass spectrometry analysis confirmed the antibody modification at two conserved regions. The compound was also applied for the labeling of other proteins such as transferrin, BSA, and an EgA1 nanobody. The conjugation was shown to be reversible using an o-phenylenediamine-based alkaline solution. This novel conjugation method offers precise and stable bioconjugation to proteins, enhancing the potential for various biomedical applications.

Wearable Biosensor Smart Glasses Based on Augmented Reality and Eye Tracking.

With the rapid development of wearable biosensor technology, the combination of head-mounted displays and augmented reality (AR) technology has shown great potential for health monitoring and biomedical diagnosis applications. However, further optimizing its performance and improving data interaction accuracy remain crucial issues that must be addressed. In this study, we develop smart glasses based on augmented reality and eye tracking technology. Through real-time information interaction with the server, the smart glasses realize accurate scene perception and analysis of the user's intention and combine with mixed-reality display technology to provide dynamic and real-time intelligent interaction services. A multi-level hardware architecture and optimized data processing process are adopted during the research process to enhance the system's real-time accuracy. Meanwhile, combining the deep learning method with the geometric model significantly improves the system's ability to perceive user behavior and environmental information in complex environments. The experimental results show that when the distance between the subject and the display is 1 m, the eye tracking accuracy of the smart glasses can reach 1.0° with an error of no more than ±0.1°. This study demonstrates that the effective integration of AR and eye tracking technology dramatically improves the functional performance of smart glasses in multiple scenarios. Future research will further optimize smart glasses' algorithms and hardware performance, enhance their application potential in daily health monitoring and medical diagnosis, and provide more possibilities for the innovative development of wearable devices in medical and health management.

Comprehensive study of CeO2/CuFe2O4 nanocomposites: Structural, EPR, magnetic, electrochemical, and cytotoxicity properties

This study dives into the successful synthesis of CeO2/CuFe2O4 nanocomposites using the auto-combustion approach and elucidates their characteristics. The electrochemical analysis of samples calcination produced at 700 °C (CeO2/CuFe2O4) revealed good results, with a specific capacitance (Cs) of 123 F/g at a current density (CD) of 0.25 A g−1 in a 1 M KOH solution. Significantly, these findings emphasize the established technique's potential for producing new, highly active, flexible, and environmentally friendly substrate materials appropriate for a variety of applications in supercapacitors. CeO2/CuFe2O4 nanocomposites may be useful in biological and medicinal research. Despite their extensive use, little study has been conducted to investigate their possible impact on cell viability, in normal cell lines. The positive benefits of the CeO2/CuFe2O4 nanocomposite structure were assessed using X-ray diffraction (XRD). To assess the impact of these nanocomposites, MTT cytotoxicity tests were performed on normal (mouse muscle fibroblast - BLO-11) cell lines. The results show that CeO2/CuFe2O4 nanocomposites have a high potential for biomedical applications, as they had no harmful effects on the cell types evaluated. As a result, the structure of the material appears to be crucial in determining both electrochemical performance and cell longevity. This discovery is significant because it provides useful insights into the morphological engineering of electrodes for a variety of applications and influences future material development.

A MnO2 nanosheets doping double crosslinked hydrogel for cartilage defect repair through alleviating inflammation and guiding chondrogenic differentiation

The inflammatory microenvironment and inferior chondrogenesis are major symptoms after cartilage defect. Although various modifications strategies associated with hydrogels exhibit remarkable capacity of pro-cartilage regeneration, the adverse effect by prolonging inflammation is still formidable to hamper potential biomedical applications of different hydrogel implants. Herein, inspired by the repair microenvironment of articular cartilage defects, an injectable, immunomodulatory, and chondrogenic L-MNS-CMDA hydrogel is prepared through grafting vinyl and catechol groups to chitosan macromolecules using amide reaction, then further loading MnO2 nanosheets (MNS). The double crosslinking of photopolymerization and catechol oxidative polymerization endows L-MNS-CMDA hydrogel with preferable mechanical property, affording a suitable mechanical support for cartilage defect repair. Additionally, the robust tissue adhesion capability stemming from catechol groups guarantees the long-term retention of the hydrogel in the defect site. Meanwhile, L-MNS-CMDA hydrogel decomposes exogenous and intracellular H2O2 into O2 and H2O, to effectively alleviate cellular oxidative stress caused by long-term hypoxia. Under the synergies of catechol groups and MNS, L-MNS-CMDA hydrogel not only inhibits macrophages polarizing into M1 phenotype, but encourages them turn into M2 phenotype, thereby, reconstructing an immunization friendly microenvironment to ultimately enhance cartilage regeneration. Predictably, the hydrogel markedly induces rat bone marrow mesenchymal stem cells differentiating into chondrocytes by expressing abundant glycosaminoglycan and type II collagen. A cartilage defect model of rat knee joint indicates that L-MNS-CMDA hydrogel visually regulate the early inflammatory response of post-implantation, and facilitate cartilage regeneration and recovery of joint function after 12 weeks of post-implantation. All in all, this multifunctional L-MNS-CMDA hydrogel exhibits superior immunomodulatory and chondrogenic properties, holding immense clinical potential in the treatment of cartilage defects.

Donor-Acceptor Type Supra-Carbon-Dots with Long Lifetime Photogenerated Radicals Boosting Tumor Photodynamic Therapy.

Carbon dots (CDs) have gained significant interest because of their potential in biomedical applications. Nevertheless, developing CDs with efficient photoinduced charge separation for tumor photodynamic therapy (PDT) remains a challenge. This study presents a novel class of supra-carbon-dots (supra-CDs) developed by fusing red emissive CDs with 2,3-dicyanohydroquinone (DCHQ) via post-solvothermal treatment. In supra-CDs, the core, acting as electron donors, is formed by assembled CDs with substantial sp2 domains, the fused interface originating from DCHQ with electron-withdrawing groups functions as the electron acceptor. This configuration creates the unique donor-acceptor nanostructure. Upon white light irradiation, the excited electrons from the assembled CDs were transferred to the electron-withdrawing interface, whereas the photogenerated holes were retained within the assembled CDs as radicals, leading to effective photoinduced charge separation. The separated photogenerated electrons then react with oxygen to generate superoxide radicals. Simultaneously, the photogenerated holes undergo oxidation of crucial cellular substrates. This dual action underscores the exceptional cell-killing efficacy of supra-CDs. Moreover, the increased particle sizes (~20 nm) ensure supra-CDs to exhibit a notable capacity for tumor accumulation via the improved permeability and retention effect, thereby achieving satisfactory anti-tumor PDT efficacy in a mouse subcutaneous tumor model.