Transferrin Immobilized Graphene Oxide Nanocomposite for Targeted Cancer Chemodynamic Therapy via Increasing Intracellular Labile Fe2+ Concentration.

Recently, different alternative regulated cell death (RCD) pathways, viz., necroptosis, pyroptosis, ferroptosis, cuproptosis etc., have been explored as important targets for the development of cancer medications in recent years, as these can change the immunogenicity of the tumor microenvironment (TME) and will finally lead to the inhibition of cancer progression and metastasis. Here, we report the development of transferrin immobilized graphene oxide (Tfn@GOAPTES) nanocomposite as a therapeutic strategy toward cancer cell killing. The electrostatic immobilization of Tfn on the GOAPTES surface was confirmed by different spectroscopy and microscopy techniques. The Tfn immobilization was found to be ∼74 ± 4%, whereas the stability of the protein on the GO surface suggested a robust nature of the nanocomposite. The MTT assay suggested that Tfn@GOAPTES exhibited cytotoxicity toward HeLa cells via increased lipid peroxidation and DNA damage. Western blot studies resulted in decreased expression of acetylation on lysine 40 of α-tubulin and increased expression of LC3a/b for Tfn@GOAPTES treated HeLa cells, suggesting autophagy to be the main cause of the cell death mechanism. Overall, we predict that the present approach can be used as a therapeutic strategy for cancer cell killing via selective induction of a high concentration of intracellular iron.

Diosgenin loaded cellulose nanoonion impedes different stages of protein aggregation induced cell death via alleviating mitochondrial dysfunction and upregulation of autophagy.

Protein aggregation is a multifaceted phenomenon prevalent in the progression of neurodegenerative diseases, yielding aggregates of diverse sizes. Recently, increased attention has been directed towards early protein aggregates due to their pronounced toxicity, largely stemming from inflammation mediated by reactive oxygen species (ROS). This study advocates for a therapeutic approach focusing on inflammation control rather than mere ROS inhibition in the context of neurodegenerative disorders. Here, we introduced Camellia sinensis cellulose nanoonion (CS-CNO) as an innovative, biocompatible nanocarrier for encapsulating the phytosteroid diosgenin (DGN@CS-CNO). The resulting nano-assembly, manifesting as spherical entities with dimensions averaging ~180-220 nm, exhibits a remarkable capacity for the gradual and sustained release of approximately 39-44 % of DGN over a 60-hour time frame. DGN@CS-CNO displays a striking ability to inhibit or disassemble various phases of hen egg white lysozyme (HEWL) protein aggregates, including the early (HEWLEA) and late (HEWLLA) stages. In vitro experiments employing HEK293 cells underscore the potential of DGN@CS-CNO in mitigating cell death provoked by protein aggregation. This effect is achieved by ameliorating ROS-mediated inflammation and countering mitochondrial dysfunction, as evidenced by alterations in TNFα, TLR4, and MT-CO1 protein expression. Western blot analyses reveal that the gradual and sustained release of DGN from DGN@CS-CNO induces autophagy, a pivotal process in dismantling intracellular amyloid deposits. In summary, this study not only illuminates a path forward but also presents a compelling case for the utilization of phytosteroid as a formidable strategy against neuroinflammation incited by protein aggregation.

Resveratrol-Encapsulated Glutathione-Modified Robust Mesoporous Silica Nanoparticles as an Antibacterial and Antibiofilm Coating Agent for Medical Devices.

The emergence of various lethal bacterial infections and their adherence to medical devices are major public health concerns. The increased bacterial exposure and titer are accompanied by the inappropriate use of antibiotics that sometimes lead to antibiotic resistance, and therefore, a drug-free antibacterial approach is required. Several nanoparticles (NPs) have been developed as antibacterial and antibiofilm coating agents, which can overcome different drug resistance mechanisms by inhibiting the important processes related to bacterial virulence potential. However, developing safe and biocompatible nanomaterials (NMs) for these applications has remained a major challenge due to their poorly understood mechanism of action. In this work, biogenic silica NPs were modified with glutathione (GSH) to form GSH@SNP (∼80 ± 15 nm) for targeting the bacterial cell surface and biofilm. GSH@SNP was loaded with resveratrol to obtain Res_GSH@SNP (∼124 ± 15 nm) that enhances the antibacterial activity of the NPs against Staphylococcus aureus and Escherichia coli by ∼51 and ∼49%, respectively, compared to GSH@SNP. Res_GSH@SNP is responsible for binding to the bacterial cell surface receptors that interrupt the cell membrane potential, leading to reactive oxygen species (ROS) generation, membrane disruption, and DNA damage and eventually resulting in antibacterial activity. Moreover, the antibiofilm activity of Res_GSH@SNP has been found to result from the interaction of the NPs with the abundant carbohydrates present on the biofilm surface. To check the practical utility of Res_GSH@SNP, these were further evaluated as an antibacterial and antibiofilm coating agent for urinary catheters and were found to be effective even after multiple washes. Res_GSH@SNP has been found to exhibit ∼80 ± 1.4% cytocompatibility toward fibroblast NIH-3T3 cells. Overall, this study is expected to pave the way for the development of biocompatible NP-based coating agents for medical devices.

Functional fluorescent nanomaterials for the detection, diagnosis and control of bacterial infection and biofilm formation: Insight towards mechanistic aspects and advanced applications.

Infectious diseases resulting from the high pathogenic potential of several bacteria possesses a major threat to human health and safety. Traditional methods used for screening of these microorganisms face major issues with respect to detection time, selectivity and specificity which may delay treatment for critically ill patients past the optimal time. Thus, a convincing and essential need exists to upgrade the existing methodologies for the fast detection of bacteria. In this context, increasing number of newly emerging nanomaterials (NMs) have been discovered for their effective use and applications in the area of diagnosis in bacterial infections. Recently, functional fluorescent nanomaterials (FNMs) are extensively explored in the field of biomedical research, particularly in developing new diagnostic tools, nanosensors, specific imaging modalities and targeted drug delivery systems for bacterial infection. It is interesting to note that organic fluorophores and fluorescent proteins have played vital role for imaging and sensing technologies for long, however, off lately fluorescent nanomaterials are increasingly replacing these due to the latter's unprecedented fluorescence brightness, stability in the biological environment, high quantum yield along with high sensitivity due to enhanced surface property etc. Again, taking advantage of their photo-excitation property, these can also be used for either photothermal and photodynamic therapy to eradicate bacterial infection and biofilm formation. Here, in this review, we have paid particular attention on summarizing literature reports on FNMs which includes studies detailing fluorescence-based bacterial detection methodologies, antibacterial and antibiofilm applications of the same. It is expected that the present review will attract the attention of the researchers working in this field to develop new engineered FNMs for the comprehensive diagnosis and treatment of bacterial infection and biofilm formation.

Erythrocyte Membrane Cloaked Cytokine Functionalized Gold Nanoparticles Create Localized Controlled Inflammation for Rapid In Vitro Wound Healing.

Due to impaired wound healing, millions of acute and chronic wound cases with increased morbidity have been recorded in the developed countries. The primary reason has been attributed to uncontrolled inflammation at the wound site, which makes healing impossible for years. The use of red blood cell (RBC) ghosts or erythrocyte membranes for different theranostic applications has gained significant attention in recent years due to their biocompatibility and biomimicking properties. Our study builds upon this concept by presenting a new approach for creating an improved and controlled inflammatory response by employing RBC ghost encapsulated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) modified AuNPs (gold nanoparticles) for accelerating the wound healing at early postinjury stage (∼48 h). The results suggested that the developed GTNFα-IL6@AuNPs created a controlled and time dependent TNF-α response and showed increased reactive oxygen species generation at ∼12 h. Further, proper M1/M2 functional transition of macrophages was observed in macrophages at different time intervals. The expression results suggested that the levels of wound healing biomarkers like transforming growth factor-ß (1.8-fold) and collagen (2.4-fold) increased while matrix metalloproteinase (3-8-fold) levels declined at later stages, which possibly increased the cell migration rate of NP treated cells to ∼90%. Hence, we are here reducing the timeline of the inflammatory phase of wound healing by actually creating a controlled inflammatory response at an early postinjury stage and further assisting in regaining the ability of cells for wound remodelation and repair. We intend that this new approach has the potential to improve the current treatment strategies for wound healing and skin repair under both in vitro and in vivo conditions.

A review on nanotechnological perspective of "the amyloid cascade hypothesis" for neurodegenerative diseases.

Neurodegenerative diseases (NDs) are characterized by progressive degeneration of neurons which deteriorates the brain functions. An early detection of the onset of NDs is utmost important, as it will provide the fast treatment strategies to prevent further progression of the disease. Conventionally, accurate diagnosis of the brain related disorders is difficult in their early phase. To solve this problem, nanotechnology based neurofunctional imaging and biomarker detection techniques have been developed which allows high specificity and sensitivity towards screening and diagnosis of NDs. Another challenge to treat the brain related disorders is to overcome the complex integrity of blood-brain-barrier (BBB) for the delivery of theranostic agents. Fortunately, utilization of nanomaterials has been pursued as promising strategy to address this challenge. Herein, we critically highlighted the recent improvements in the field of neurodiagnostic and therapeutic approaches involving innovative strategies for diagnosis, and inhibition of protein aggregates. We have provided particular emphasis on the use of nanotechnology which can push forward the blooming research growth in this field to win the battle against devastating NDs.

Antibody-conjugated nanoparticles for target-specific drug delivery of chemotherapeutics.

Nanotechnology provides effective methods for precisely delivering chemotherapeutics to cancer cells, thereby improving efficacy and reducing off-target side effects. The targeted delivery of nanoscale chemotherapeutics is accomplished by two different approaches, namely the exploitation of leaky tumor vasculature (EPR effect) and the surface modification of nanoparticles (NPs) with various tumor-homing peptides, aptamers, oligonucleotides, and monoclonal antibodies (mAbs). Because of higher binding affinity and specificity, mAbs have received a lot of attention for the detection of selective cancer biomarkers and also for the treatment of various types of cancer. Antibody-conjugated nanoparticles (ACNPs) are an effective targeted therapy for the efficient delivery of chemotherapeutics specifically to the targeted cancer cells. ACNPs combine the benefits of NPs and mAbs to provide high drug loads at the tumor site with better selectivity and delivery efficiency. The mAbs on the NP surfaces recognize their specific receptors expressed on the target cells and release the chemotherapeutic agent in a controlled manner. Appropriately designed and synthesized ACNPs are essential to fully realize their therapeutic benefits. In blood stream, ACNPs instantly interact with biological molecules, and a protein corona is formed. Protein corona formation triggers an immune response and affects the targeting ability of the nanoformulation. In this review, we provide recent findings to highlight several antibody conjugation methods such as adsorption, covalent conjugation, and biotin-avidin interaction. This review also provides an overview of the many effects of the protein corona and the theranostic applications of ACNPs for the treatment of cancer.

Carbon nanosphere based bifunctional oxidoreductase nano-catalytic agent to mitigate hypoxia in cancer cells.

Developing metal-free carbon nanozyme for tumor hypoxia is difficult. In biomedical applications, especially in the case of biomolecular detection, extensive research has been done on nanozymes with enzyme-mimicking catalytic activity. However, there are considerably fewer investigations on targeted nano-catalytic tumor therapy. Nano catalytic medicine-enabled chemotherapy is a safe and promising treatment strategy that involves the conversion of excess H2O2 into O2 in a tumor environment. Here we have synthesized carbon nanosphere (CNS) using the Camellia sinensis plant (CS-CNS). Further surface functionalization was achieved via nitrilotriacetic acid conjugation (NTA@CS-CNS). A stability study of synthesized nanozyme in the presence of various cations, anions, and 5 different pH range suggested the robustness of carbon based nanoassembly. The catalytic in vitro study shows that NTA@CS-CNS mimics peroxidase and catalase using TMB and H2O2 as substrates. NTA@CS-CNS showed Km and Vmax values of ~ 193.2 µM and 0.43 µM/s, ~ 413 µM and 1.42 µM/s, and ~ 378 µM and 1.63 µM/s, respectively when H2O2 and TMB was used for CAT and POD activity. Results showed that NTA@CS-CNS in combination with SFN and laser irradiation reduces hypoxia. Hence, our study could pave the path for the development of different non-toxic nano catalytic therapy for tumors in cancerous cells.

Charged Gold Nanoparticles Promote In Vitro Proliferation in Nardostachys jatamansi by Differentially Regulating Chlorophyll Content, Hormone Concentration, and Antioxidant Activity.

Nardostachys jatamansi is a critically endangered medicinal plant and endemic to the Himalayas, having high commercial demand globally. The accumulation of various secondary metabolites in its shoots and roots with antioxidant potential are well-documented in traditional as well as modern medicine systems. In the present study, we first attempted to investigate the impact of citrate (-ve charge, 11.1 ± 1.9 nm) and CTAB (+ve charge, 19.5 ± 3.2 nm) coated gold nanoparticles (AuNPs) on the in vitro proliferation and antioxidant activities of N. jatamansi. Both the nanoparticles differentially affected the morphological and biochemical parameters, chlorophyll content, internal hormone concentration, and antioxidant activities in a concentration-dependent (10-100 µM) manner. Vigorous shooting was observed in half strength MS medium supplemented with IAA (1 mg/L) with 60 µM citrate-AuNPs (46.4 ± 3.7 mm) and 40 µM CTAB-AuNPs (42.2 ± 3.2 mm). Similarly, the maximum number of roots (5.00 ± 0.67 and 5.33 ± 0.58) and root length (29.9 ± 1.5 mm and 27.3 ± 4.8 mm) was reported in half-strength MS medium with IAA (1 mg/L) supplemented with 60 µM citrate-AuNPs and 40 µM CTAB-AuNPs, respectively. In addition, plants growing on MS medium supplemented with 60 µM citrate-AuNPs and 40 µM CTAB-AuNPs showed significantly enhanced photosynthetic pigments (chlorophyll a and b, carotenoids, and total chlorophyll), internal hormone concentration (GA3, IAA, and ABA), and antioxidant activities (total phenolics, flavonoids, DPPH, and SOD enzyme activity). Moreover, the transcript analysis of ANR1, ARF18, PLY9, SAUR28, GID1A, GRF1, SOD, and CAT further confirmed the role of 60 µM citrate-AuNPs and 40 µM CTAB-AuNPs in the improvement in the growth and antioxidant activities of N. jatamansi. Bearing in mind the urgent requirements of the effective conservation measures of this endangered species, the present findings suggest the elicitation of citrate-AuNPs and CTAB-AuNPs would significantly improve the potential applications of N. jatamansi in the medicinal plant-based industry.

Single-walled carbon nanotube conjugated cytochrome c as exogenous nano catalytic medicine to combat intracellular oxidative stress.

Mitochondrial dysfunction has been reported to be one of the main causes of many diseases including cancer, type2 diabetes, neurodegenerative disorders, cardiac ischemia, sepsis, muscular dystrophy, etc. Under in vitro conditions, Cytochrome C (Cyt C) maintains mitochondrial homeostasis and stimulates apoptosis, along with being a key participant in the life-supporting function of ATP synthesis. Hence, the medicinal importance of Cyt C as catalytic defense is immensely important in various mitochondrial disorders. Here, we have developed a nanomaterial via electrostatically conjugating oxidized single-wall carbon nanotube with Cyt C (Cyt C@cSWCNT) for the exogenous delivery of Cyt C. The chemical and morphological characterization of the developed Cyt C@cSWCNT was done using UV-vis, FTIR, XPS, powder XRD, TGA/DSC, TEM, etc. The developed Cyt C@cSWCNT exhibited bifunctional catalase and peroxidase activity with Km (∼ 642.7 µM and 351.6 µM) and Vmax (∼0.33 µM/s and 2.62 µM/s) values, respectively. Also, through this conjugation Cyt C was found to retain its catalytic activity even at 60 °C, excellent catalytic recyclability (at least up to 3 times), and wider pH activity (pH = 3 to 9). Cyt C@cSWCNT was found to promote intracellular ROS quenching and maintain mitochondrial membrane potential and cellular membrane integrity via Na+/K+ ion homeostasis during the H2O2 stress. Overall the present strategy provides an alternative approach for the exogenous delivery of Cyt C which can be used as nano catalytic medicine.

Facile synthesis of biogenic silica nanomaterial loaded transparent tragacanth gum hydrogels with improved physicochemical properties and inherent anti-bacterial activity.

In this report, biogenic, crystalline (∼60.5 ± 2%) bowknot structured silica nanoparticles (BSNPs) of length ∼ 274 ± 7 nm and width ∼ 36 ± 2 nm were isolated from invasive species viz. Lantana camara. These were then chemically modified using nitrogen containing moieties viz. APTES and CTAB. These modified BSNPs were then used as electrostatic cross-linking agents for the formation of tragacanth gum (TG) hydrogels. The cytocompatible CTAB@BSNP-TG hydrogels documented ∼10-12 fold enhancement in anti-bacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa when compared with TG hydrogels. Disruption of the bacterial membrane by ROS generation and protein leakage were responsible for anti-bacterial activity. A cell migration assay suggested that CTAB@BSNP-TG augmented the cell proliferation of NIH-3T3 cells compared to other TG hydrogels. The present study will pave the path for the development of organic-inorganic hybrid nanocomposite-based hydrogels for anti-bacterial and cell migration applications.

Protein-Cloaked Nanoparticles for Enhanced Cellular Association and Controlled Pathophysiology via Immunosurveillance Escape.

Weak interactions play an important role in soft corona (SC) formation and thus help in evaluating the biological fate of the nanoparticles (NPs). Preadsorption of specific proteins on the NP surface, leading to SC formation, has been found to help NPs in evading immunosurveillance. However, the role of different preadsorbed biomolecules in determining the NP pathophysiology and cellular association, upon their re-exposure to in vivo conditions, still remains elusive. Here, differently charged gold NPs were precoated with two different blood components, viz. red blood cells and human serum albumin protein, and these were then re-exposed to human serum. Cloaking NPs with protein improved the NP colloidal stability and other physico-chemical properties along with increased cellular association. Detailed proteomic analysis suggested that protein-camouflaged NPs showed a decrease in immune-responsive proteins compared to their bare counterparts. Further, it was also observed that the secondary protein signature on the NP surface was governed by primary protein coating; however, the event was more or less NP charge-independent. This study will pave the path for future strategies to make NPs invincible to the immunosurveillance system of the body.

The curious cases of nanoparticle induced amyloidosis during protein corona formation and anti-amyloidogenic nanomaterials: Paradox or prejudice?

Protein corona (PC) formation remains a major hurdle in the successful delivery of nanomedicines to the target sites. Interacting proteins have been reported to undergo structural changes on the nanoparticle (NP) surface which invariably impacts their biological activities. Such structural changes are the result of opening of more binding sites of proteins to adsorb on the NP surface. The process of conversion of α-helix proteins to their ß-sheet enriched counterpart is termed as amyloidosis and in case of PC formation, NPs apparently play the crucial role of being the nucleation centres where this process takes place. Conversely, increasing numbers of artificial nano-chaperones are being used to treat the protein misfolding disorders. Anti-amyloidogenic nanomaterials (NM) have been gaining utmost importance in inhibiting Aß42 (hallmark peptide for Alzheimer's disease) and Hen egg white lysozyme (HEWL, model protein for systemic amyloidosis) aggregation. Interestingly, in this process, NPs inhibit protein ß-sheet enrichment. These two seemingly opposite roles of NPs, propelling confirmatory change onto the smorgasbord of adsorbed native proteins and the ability of NPs in inhibiting amyloidosis creates a paradox, which has not been discussed earlier. Here, we highlight the key points from both the facets of the NP behaviour with respect to their physicochemical properties and the nature of proteins they adsorb onto them to unravel the mystery. BRIEF: Protein corona formation remains a major hurdle in achieving the desired efficacy of nanomedicine. Proteins when interact with nanoparticle (NP) surface, undergo both structural and biological changes. Again, NPs are known to exhibit anti-amyloidogenic behaviour where these play the crucial role of preventing any change in their native structure. Such seemingly different roles of NPs need sincere inquisition.

Multifunctional Gold Nanoparticle-Conjugated Cellulose Nanoonions Alleviate Aß42 Fibrillation-Induced Toxicity via Regulation of Oxidative Stress and Ion Homeostasis.

Inhibition of hen egg white lysozyme (HEWL) and Aß42 fibrillation have been established as the main models for the treatment of systemic lysozyme amyloidosis and Alzheimer's disease (AD), respectively. Several antiamyloidogenic nanomaterials have been developed over the period; however, their intracellular mechanism of action is still not well understood. In this context, plant-based, gold-conjugated, injectable, hydrophilic cellulose nanoonions (CNOs), viz., DH-CNO (∼60 ± 5 nm) and LC-CNO (∼55 ± 12 nm), were developed from their respective hydrophobic cellulose nanocrystals (DH-CNC and LC-CNC) using a single-step chemical template-mediated process. This unique nanocellulose architecture was chemically and morphologically characterized by various spectroscopic and microscopic techniques. Further, the different biophysical studies documented marked the inhibition/disintegration potential of gold-conjugated LC-CNO against HEWL and Aß42 peptide aggregation. It was further observed that inhibition of protein fibrillation could be achieved within ∼10 min when the same materials were used under photoirradiation conditions. In vitro protein aggregation studies using HEK293 cells suggested that gold-conjugated LC-CNO could effectively reduce the cellular toxicity via regulation of oxidative stress and ion homeostasis. The outcome of the present study will help in designing cellulose-based novel functional nanochaperones against various neurodegenerative diseases.

Bioinspired Metal-Free Fluorescent Carbon Nanozyme with Dual Catalytic Activity to Confront Cellular Oxidative Damage.

Development of metal-free, recyclable enzyme mimics is challenging and requires key chemical modifications at the molecular level. Here, nitrilotriacetic acid-functionalized carbon nanospheres (LC-CNS@NTA) were prepared from the nitrogen-rich weed Lantana camara (LC) using a simple hydrothermal reaction condition. Transmission electron microscopy (TEM) studies revealed size of ∼160 ± 20 nm for LC-CNS@NTA whereas, the same showed fluorescence emission at ∼520 nm with a ∼63% quantum yield. Furthermore, LC-CNS@NTA showed strong peroxidase (Pxrd) activity toward a wide range of substrate viz., H2O2, 3,3',5,5'-tetramethylbenzidine, and o-phenylenediamine with Km and Vmax values of ∼257 µM and 1.06 µM/s, 282 µM and 1.47 µM/s, and 270.8 µM and 1.647 µM/s, respectively. Interestingly, this also showed catalase (CAT) activity against H2O2 with Km and Vmax values of ∼0.374 µM and 1.87 µM/s, respectively. It was observed that LC-CNS@NTA could effectively reduce the oxidative stress-induced cytotoxicity of HEK293 cells via retention of mitochondrial membrane potential, prevention of lipid peroxidation and DNA damage. It was further found that LC-CNS@NTA-treated cells showed reduced level of intracellular protein carbonylation and protein aggregation. The finding of the present study is expected to pave the path for designing engineered metal-free carbon nanozyme with dual enzyme mimic activity.

Inhibition of Glycation-Induced Aggregation of Human Serum Albumin by Organic-Inorganic Hybrid Nanocomposites of Iron Oxide-Functionalized Nanocellulose.

Protein aggregation leads to the transformation of proteins from their soluble form to the insoluble amyloid fibrils and these aggregates get deposited in the specific body tissues, accounting for various diseases. To prevent such an aggregation, organic-inorganic hybrid nanocomposites of iron oxide nanoparticle (NP, ∼6.5-7.0 nm)-conjugated cellulose nanocrystals (CNCs) isolated from Syzygium cumini (SC) and Pinus roxburghii (PR) were chemically synthesized. Transmission electron microscopy (TEM) images of the nanocomposites suggested that the in situ-synthesized iron oxide NPs were bound to the CNC surface in a uniform and regular fashion. The ThT fluorescence assay together with 8-anilino-1-naphthalenesulfonic acid, Congo Red, and CD studies suggested that short fiber-based SC nanocomposites showed better inhibition as well as dissociation of human serum albumin aggregates. The TEM and fluorescence microscopy studies supported similar observations. Native polyacrylamide gel electrophoresis results documented dissociation of higher protein aggregates in the presence of the developed nanocomposite. Interestingly, the dissociated proteins retained their biological function by maintaining a high amount of α-helix content. The in vitro studies with HEK-293 cells suggested that the developed nanocomposite reduces aggregation-induced cytotoxicity by intracellular reactive oxygen species scavenging and maintaining the Ca2+ ion-channel. These results indicated that the hybrid organic-inorganic nanocomposite, with simultaneous sites for hydrophobic and hydrophilic interactions, tends to provide a larger surface area for nanocomposite-protein interactions, which ultimately disfavors the nucleation step for fibrillation for protein aggregates.

Molecular recognition based rapid diagnosis of immunoglobulins via proteomic profiling of protein-nanoparticle complexes.

Protein-nanoparticle (NP) interaction, which inevitably form protein corona (PC), has been the subject of much debate about its role in modern biomedical research. In this regard, PC associated with two different NPs viz., magneto-fluorescent (MF) and chitosan coated MF (CMF) NPs were thoroughly investigated, to analyze the effect of polymer coating on protein adsorption. Bradford assay, along with the spectroscopic and microscopic studies suggested increase in adsorbed protein quantity, though the results varied significantly on moving from bare to polymeric coating and in vitro to ex vivo conditions. Interestingly, polymer coated NPs showed increased protein adsorption and induce minimal changes in protein structural integrity under the same conditions. We predict that the changes in secondary structure of primary corona determine the overall signature of surface binding proteins in PC. Our findings suggested that rapid diagnosis of immunoglobulins is possible using the concept of protein corona formation ex vivo.

Nanomaterials as potential and versatile platform for next generation tissue engineering applications.

Tissue engineering (TE) is an emerging field where alternate/artificial tissues or organ substitutes are implanted to mimic the functionality of damaged or injured tissues. Earlier efforts were made to develop natural, synthetic, or semisynthetic materials for skin equivalents to treat burns or skin wounds. Nowadays, many more tissues like bone, cardiac, cartilage, heart, liver, cornea, blood vessels, and so forth are being engineered using 3-D biomaterial constructs or scaffolds that could deliver active molecules such as peptides or growth factors. Nanomaterials (NMs) due to their unique mechanical, electrical, and optical properties possess significant opportunities in TE applications. Traditional TE scaffolds were based on hydrolytically degradable macroporous materials, whereas current approaches emphasize on controlling cell behaviors and tissue formation by nano-scale topography that closely mimics the natural extracellular matrix. This review article gives a comprehensive outlook of different organ specific NMs which are being used for diversified TE applications. Varieties of NMs are known to serve as biological alternatives to repair or replace a portion or whole of the nonfunctional or damaged tissue. NMs may promote greater amounts of specific interactions stimulated at the cellular level, ultimately leading to more efficient new tissue formation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2433-2449, 2019.

Toxicity Concerns of Therapeutic Nanomaterials.

In the modern era, research on the synthesis of nanoparticles (NPs) has been growing exponentially. Due to their small size together with extra-ordinary physico-chemical properties, a variety of NPs i.e., metallic, carbon-based, fluorescent, and polymer-based have been exploited in different fields such as tissue engineering, drug delivery, and various other therapeutic applications. Instead of multi-disciplinary applications of NPs, research dealing with the toxicity concerns and influence of such materials, on the public health, plants and environment is still in its infancy. NPs can cause damage at the cellular, sub-cellular, molecular and protein levels owing to their extremely small size, large surface area to volume ratio, shape, and surface functionality. The present review is aimed to provide wide-ranging information related to NPs toxicology, the mechanisms of action, routes of their entry into the body and probable impacts on human health. Understanding of NPs entry routes into the body entails further research so as to update policymakers and regulatory bodies about the toxicity concerns associated with these nanomaterials. Proper characterization of NPs, factors affecting uptake and toxicity of NPs, as well as an understanding of processes when NPs come in contact with living beings, is critical to estimate the possible hazards.

Engineered Bright Blue- and Red-Emitting Carbon Dots Facilitate Synchronous Imaging and Inhibition of Bacterial and Cancer Cell Progression via 1O2-Mediated DNA Damage under Photoirradiation.

The development of biocompatible, widely applicable fluorescent imaging probe, with emission beyond the cellular and tissue autofluorescence interference, is a challenging task. In this regard, a series of 28 different fluorescent carbon dots (CDs) were synthesized using carbohydrates as carbon and cysteine (Cys) and o-phenylenediamine (OPD) as nitrogen source. The screened CDs showed photostability with bright blue (∼505-520 nm) and red (∼588-596 nm) emission and high fluorescence quantum yield (QY = 72.5 ± 4.5%). FTIR and NMR studies suggested presence of carboxylate and ester group for Cys- and OPD-based CDs, respectively. HRTEM results showed particle size of ∼3.3-5.8 nm for all the developed CDs. The antibacterial studies suggested that the developed CDs showed preferential antibacterial activity against Escherichia coli, with IC50 value of ∼200 µg/mL. Cytotoxicity and confocal microscopy studies of HeLa cells reflected that these CDs showed both anticancer activity and imaging ability. Agarose gel electrophoresis, together with SOSG assay and thiol estimation studies, suggested oxidative stress induced DNA degradation to be the primary cause for cell death. These hemocompatible CDs can thus be used as simultaneous imaging probe and photo dynamic therapeutic agent for both antibacterial and anticancer activity.