Bioconjugated Nanoparticles Research Articles

The Biogenetic Synthesis of Metallic Nanoparticles and the Role they Play in the Anti-inflammatory Drug Treatment.

Nanoscience and nanotechnology have resulted in the continuous development of new nanomaterials with remarkable properties that make them appealing for pharmaceutical applications. The biocompatibility of metallic nanoparticles is of increasing interest for research scientists currently working towards developing novel nano-based medicines, industrial chemicals, and antigens. There is also a particular interest in using them to counter mutations that up-regulate inflammation enhancers to produce a range of inflammation-related pathologies. The following review discusses the anti-inflammatory mechanisms of metallic bioconjugated (silver, gold, zinc oxide, titanium dioxide, and selenium) nanoparticles. The current study focuses on nanoparticle manufacturing technologies and the inflammatory response. A thorough search was conducted in several databases, including Scopus, Embase, Cochrane, and PubMed. The search terms used included: Alzheimer's disease, mechanism of action, neuroinflammation, the reaction of Mast cells to stress and neuroinflammation. The study included all publications published in English. Green-synthesised nanoparticles can suppress the NF-B and cyclooxygenase-2 pathways, preventing the production of proinflammatory cytokines and ROS scavenging mechanisms. Metallic nanoparticles with anti-inflammatory properties, such as stability and specific targeting, have been briefly discussed. The current research focuses on metallic nanoparticles employed as anti-inflammatory medication molecules, although nanoparticles have applications in various areas (medicine, chemical engineering, and agriculture). Nanoparticles have a large surface-to-volume ratio, which can help them to penetrate cell membranes, and because of their solid ligand-binding capabilities, nanoparticles have been used in the medical treatment of inflammatory pathologies.

DNA conformational change embrace ultraviolet photolysis: A dual-mode sensing platform for electrochemical and fluorescent signaling

We developed a dual-mode biosensor that utilizes DNA conformational changes and ultraviolet photolysis for electrochemical (EC) and fluorescence (FL) detection. In this study, a stem-loop-structured carcinoembryonic antigen (CEA) aptamer was modified on an Au electrode, and this aptamer contained a redox-labeled methylene blue (MB), short-chain DNA with a 6-carboxylic fluorescein (FAM) and a PC linker that can be cleaved by ultraviolet light. Subsequently, CEA and CEA antibody-modified upconversion nanoparticle bioconjugates (CEA-Ab@UCNPs) were added. In the presence of CEA, Ab@UCNPs can bind CEA and push the MB which was originally close to the electrode surface, away from the electrode surface, resulting in a reduced redox current. Under irradiation with a 980 nm laser, the UCNPs emit ultraviolet light, leading to photocleavage of the PC linker and the release of FAM for FL sensing. Under optimal conditions, the EC and FL modes showed good responses to CEA within 0.01–50 ng/mL and 0.1–80 ng/mL, respectively.

Multivalent nanobody engineering for enhanced physisorption and functional display on gold nanoparticles.

The ease of expression and engineering of single domain antibodies, known as nanobodies, make them attractive alternatives to conventional antibodies in point-of-care diagnostics such as lateral flow assays. In lateral flow assays, gold nanoparticle bioconjugates serve as labels which display affinity molecules on the gold surface. While examples of nanobody gold nanoparticle bioconjugates exist, few utilise the simple one-step approach of physisorption owing to undesirable nanoparticle aggregation and loss of functionality. Here we show that engineering nanobodies into multivalent structures can significantly enhance their functionality when physisorbed onto gold nanoparticles. This approach enables resulting bioconjugates to withstand multiple processing steps required for long-term nanoparticle storage within lateral flow assays. Specifically, we show that the trivalent version of VHHV nanobody (VHH3) against the S1 protein of SARS-CoV-2 can be immobilised onto gold nanoparticles through passive adsorption. Unlike its monovalent and bivalent nanobody counterparts, using VHHV3 preserves nanoparticle stability under salt stress, blocking, washing, and freeze-drying conditions while maintaining picomolar sensitivity to the S1 protein. We anticipate that this facile strategy is a significant advancement towards the integration of nanobodies in lateral flow assay development.

Methods gold standard in clinic millifluidics multiplexed extended gate field-effect transistor biosensor with gold nanoantennae as signal amplifiers

We present a portable multiplexed biosensor platform based on the extended gate field-effect transistor and demonstrate its amplified response thanks to gold nanoparticle-based bioconjugates introduced as a part of the immunoassay. The platform comprises a disposable chip hosting an array of 32 extended gate electrodes, a readout module based on a single transistor operating in constant charge mode, and a multiplexer to scan sensing electrodes one-by-one. Although employing only off-the-shelf electronic components, our platform achieves sensitivities comparable to fully customized nanofabricated potentiometric sensors. In particular, it reaches a detection limit of 0.2 fM for the pure molecular assay when sensing horseradish peroxidase-linked secondary antibody (∼0.4 nM reached by standard microplate methods). Furthermore, with the gold nanoparticle bioconjugation format, we demonstrate ca. 5-fold amplification of the potentiometric response compared to a pure molecular assay, at the detection limit of 13.3 fM. Finally, we elaborate on the mechanism of this amplification and propose that nanoparticle-mediated disruption of the diffusion barrier layer is the main contributor to the potentiometric signal enhancement. These results show the great potential of our portable, sensitive, and cost-efficient biosensor for multidimensional diagnostics in the clinical and laboratory settings, including e.g., serological tests or pathogen screening.

Biosynthetically produced glucose oxidase immobilized silver nanoparticle bioconjugate treatment improves the shelf life of mango fruit: an innovative method towards food safety and sustainability

Biosynthetically produced glucose oxidase immobilized silver nanoparticle bioconjugate treatment improves the shelf life of mango fruit: an innovative method towards food safety and sustainability

Biocompatibility assessment of Rutin and PEG loaded novel nanoceria on human erythrocytes and human myeloid leukemia (U937) cells

Nanomaterials are increasingly being used, prompting extensive research into nanomedicine. The use of nanomaterials is constrained by the absence of comprehensive toxicity profiles, despite their impressive diagnostic and therapeutic outcomes in in vitro and in vivo models. The compatibility of the bioconjugate nanoparticles, we fabricated a novel Rutin (Rut) and polyethylene glycol (PEG) loaded cerium oxide nanoparticles (Rut-PEG-CeO2NPs). The investigation of antibacterial activity of cerium oxide nanoparticles (CeO2NPs), Rut, Rut-PEG-CeO2 NPs and antibiotic was examined against Gram-positive and Gram-negative pathogens using well-diffusion and time-kill assays. The fabricated Rut-PEG-CeO2NPs has demonstrated broad spectrum nature resulting in significant cell damage at the target site when compared to CeO2NPs and Rut. The haemolytic effect of Rut-PEG-CeO2NPs on erythrocytes from healthy donor (HDE) and diabetic donor (DDE) was evaluated using the haemolysis assay against CeO2NPs. The results exhibit that the percentage of haemolysis was more in DDE compared to that of HDE for CeO2NPs as well as Rut-PEG-CeO2NPs. The study of anticoagulation activity using plasma recalcification time method which shows the clotting time of platelet rich plasma (PRP) 280–290 s and platelet poor plasma (PPP) 245–318 s. Besides that, the anti-angiogenetic property was evaluated using chick embryo chorioallantoic membrane (CAM) assay which showed the remarkable anti-angiogenic effect of Rut-PEG-CeO2NPs on the chick embryo. Additionally, the in vitro cytotoxicity of Rut-PEG-CeO2NPs was tested on human myeloid leukemia cells (U937) against Rut and CeO2NPs. The cytotoxicity results depicted that Rut-PEG-CeO2NPs shows high percent of cell viability compared to that of CeO2NPs and Rutin. These results suggests that the fabricated Rut-PEG-CeO2NPs has novel approach towards the therapeutic applications which is potentially due to the loading of Rut on the CeO2NPs on the surface to form Rut-PEG-CeO2NPs.

Deep learning for the encounter of inorganic nanomaterial for efficient photochemical hydrogen production

A strong photosynthetic multifaceted called photosystem I (PS I) successfully catches photons to produce a charge detached phase through a quantum yield. The low latent reductant that is created is dignified at a redox potential that is conducive to H2 development, and this charge detached phase is constant for around 100 ms. By using dithiol as a molecular wire to link Photo System I to the particles and transport electrons as of the incurable electron transport cofactor of Photo System I, towards the nanoparticle, PS I consumes been covalently connected to the surfaces of like as Pt and also Au nanoparticles. The Photosystem I or molecular wire or nanoparticle bio conjugates are capable of catalysing the reaction 2H+ + 2e H2 when illuminated. H2 development is not slowed down by the transference of electrons from PS I in the direction of the nanoparticle via the molecular wire. The speed of H2 evolution is increased fivefold when the system is supplied by means of more effective donor sideways electron-donating kinds. When evaluating hydrogen production based on predicted energy from the sun with observed values falling on unstable slopes, the root mean square error called as RMSE as well as coefficient of determination called R2 are utilised as performance metrics. The most effective model among those taken into consideration, the Deep Learning model performs well and is quite compatible with the observational data.

Differences in the Cell Type-Specific Toxicity of Diamond Nanoparticles to Endothelial Cells Depending on the Exposure of the Cells to Nanoparticles.

Diamond nanoparticles are considered to be one of the most cytocompatible carbon nanomaterials; however, their toxicity varies significantly depending on the analysed cell types. The aim was to investigate the specific sensitivity of endothelial cells to diamond nanoparticles dependent on exposure to nanoparticles. Diamond nanoparticles were characterized with Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS). Toxicity of diamond nanoparticles was assessed for endothelial cells (HUVEC), human mammary epithelial cells (HMEC) and HS-5 cell line. The effect of diamond nanoparticles on the level of ROS, NO, NADPH and protein synthesis of angiogenesis-related proteins of endothelial cells was evaluated. Our studies demonstrated severe cell type-specific toxicity of diamond nanoparticles to endothelial cells (HUVEC) depending on nanoparticle surface interaction with cells. Furthermore, we have assessed the effect on cytotoxicity of the bioconjugation of nanoparticles with a peptide containing the RGD motive and a serum protein corona. Our study suggests that the mechanical interaction of diamond nanoparticles with the endothelial cell membranes and the endocytosis of nanoparticles lead to the depletion of NADPH, resulting in an intensive synthesis of ROS and a decrease in the availability of NO. This leads to severe endothelial toxicity and a change in the protein profile, with changes in major angiogenesis-related proteins, including VEGF, bFGF, ANPT2/TIE-2, and MMP, and the production of stress-related proteins, such as IL-6 and IL-8. We confirmed the presence of a relationship between the toxicity of diamond nanoparticles and the level of cell exposure to nanoparticles and the nanoparticle surface. The results of the study give new insights into the conditioned toxicity of nanomaterials and their use in biomedical applications.

Behind the Optimization of the Sensor Film: Bioconjugation of Triangular Gold Nanoparticles with Hemoproteins for Sensitivity Enhancement of Enzymatic Biosensors.

Electrochemical biosensors are widely used in a multitude of applications, such as medical, nutrition, research, among other fields. These sensors have been historically used and have not undergone many changes in terms of the involved electrochemical processes. In this work, we propose a new approach on the immobilization and enhancement of the electrochemical properties of the sensing layers through the control and bioconjugation of hemoproteins (hemoglobin, myoglobin, and cytochrome C) on anisotropic gold nanoparticles (gold nanotriangles (AuNTs)). The hemeproteins and the AuNTs are mixed in a solution, resulting in stable bioconjugates that are deposited onto the electrode surface to obtain the biosensors. All the systems proposed herein exhibited direct well-defined redox responses, highlighting the key role of the AuNTs acting as mediators of such electron transfers. Several protein layers surrounding the AuNTs are electroactive, as demonstrated from the charge measured by cyclic voltammetry. The retention of the stability of the hemeproteins once they are part of the bioconjugates is evidenced towards the electrocatalytic reduction of hydrogen peroxide, oxygen, and nitrite. The parameters obtained for the proposed biosensors are similar or even lower than those previously reported for similar systems based on nanomaterials, and they exhibit attractive properties that make them potential candidates for the latest developments in the field of sensing devices.

Lanthanide-Doped Inorganic Nanoprobes for Luminescent Assays of Biomarkers

ConspectusTremendous progress in nanomaterial and nanotechnology has been made in recent years, which greatly contributes to the development of inorganic nanoparticles (NPs) as luminescent probes in diverse biomedical applications. In particular, these luminescent nanoprobes are widely employed for sensitive assays of biomarkers like disease markers. Generally, the luminescent bioassay technologies mainly rely on conventional molecular probes such as lanthanide (Ln3+) chelates or organic dyes, which suffer from inferior photochemical stability, low photobleaching, potential long-term toxicity, or high background noise. In contrast, Ln3+-doped NPs possess distinct physicochemical properties including better photostability, lower toxicity, and superior optical properties like long photoluminescent (PL) lifetime, narrow emission band, and tunable spectral range from the ultraviolet to the second near-infrared (NIR-II), which make them extremely ideal as luminescent nanoprobes. As such, enormous research enthusiasm has been invested in this fascinating field of Ln3+-doped luminescent nanoprobes in recent years. Accordingly, background-free luminescent bioassays with high signal-to-noise have been achieved by employing Ln3+-doped NPs on the basis of their downshifting luminescence (DSL) with a long PL lifetime, NIR-II luminescence with long-wavelength emissions, or upconverting luminescence (UCL) upon NIR excitation. However, there are still key challenges for Ln3+-doped nanoprobes owing to their low brightness and quantum yield, which restrict their biomedical applications. During the past decade, we have explored efficient approaches for the synthesis and design of highly efficient Ln3+-doped nanoprobes toward ultrasensitive luminescent bioassay of disease markers.In this Account, we summarize our most recent endeavors toward the development of inorganic Ln3+-doped NPs as sensitive nanoprobes for luminescent bioassays. First, we overview the approaches of controlled synthesis and optical manipulation to obtain highly efficient Ln3+-doped NPs with desirable optical properties. Second, we survey the design of Ln3+-doped nanoprobes with outstanding water dispersibility and excellent biocompatibility through surface functional bioconjugation of NPs. By employing these nanoprobes, we propose and exemplify several background-free luminescent bioassay strategies in an effort to suppress the interference of background noise from scattered lights and autofluorescence from biological samples. Third, we highlight the ultrasensitive bioassay of disease markers such as the time-resolved luminescent bioassay, NIR-II luminescent bioassay, and UCL bioassay. Finally, the major challenges, promising emerging trends, and future perspectives on this attractive field are discussed. Through this Account, we aim to offer a series of effective approaches to luminescent bioassay with high sensitivity and excellent specificity based on Ln3+-doped nanoprobes, which may broaden the roadway for clinical bioassays and accelerate the exploration of novel nanoprobes in versatile biomedical applications.

Light and immunostimulant mediated in situ re-education of tumor-associated macrophages using photosensitizer conjugated mannan nanoparticles for boosting immuno-photodynamic anti-metastasis therapy.

In an immunosuppressive tumor microenvironment, tumor-associated macrophages (TAMs) are the most abundant cells displaying pro-tumorigenic M2-like phenotypes, encouraging tumor growth and influencing the development of resistance against conventional therapies. TAMs are highly malleable. They can be repolarized into tumoricidal M1-like cells. In this study, we report the synthesis of novel co-operative immuno-photodynamic nanoparticles involving TAM self-targeting acrylic acid grafted mannan (a polysaccharide) conjugated with the chlorin e6 (Ce6) photosensitizer and then loaded with resiquimod (R848), a toll-like receptor (TLR7/8) agonist. The mannan conjugated Ce6 loaded with R848 (MCR) as bioconjugate nanoparticles demonstrated selective targeting of anti-inflammatory M2-like cells. Using photodynamic therapy they were repolarized to pro-inflammatory M1-like cells with combined effects of reactive oxygen species (ROS)-triggered intracellular signaling and a small-molecule immunostimulant. The MCR also demonstrated a TAM-directed adaptive immune response, inhibited tumor growth, and prevented metastasis. Our results indicate that these MCR nanoparticles can effectively target TAMs and modulate them for cancer immunotherapy.

A Gold Nanoparticle Bioconjugate Delivery System for Active Targeted Photodynamic Therapy of Cancer and Cancer Stem Cells.

Simple SummaryCancer stem cells (CSCs) play a crucial role in tumor development, metastasis, therapy resistance, and relapse due to their self-renewal and proliferative potential. In this review, we summarized the application of gold nanoparticle (AuNPs) bioconjugates in enhancing the efficiency of photodynamic therapy (PDT) in cancer and CSCs. We also highlighted the challenges facing the translation of AuNPs application in clinical settings.Cancer stem cells (CSCs), also called tumor-initiating cells, are a subpopulation of cancer cells believed to be the leading cause of cancer initiation, growth, metastasis, and recurrence. Presently there are no effective treatments targeted at eliminating CSCs. Hence, an urgent need to develop measures to target CSCs to eliminate potential recurrence and metastasis associated with CSCs. Cancer stem cells have inherent and unique features that differ from other cancer cells, which they leverage to resist conventional therapies. Targeting such features with photodynamic therapy (PDT) could be a promising treatment for drug-resistant cancer stem cells. Photodynamic therapy is a light-mediated non-invasive treatment modality. However, PDT alone is unable to eliminate cancer stem cells effectively, hence the need for a targeted approach. Gold nanoparticle bioconjugates with PDT could be a potential approach for targeted photodynamic therapy of cancer and CSCs. This approach has the potential for enhanced drug delivery, selective and specific attachment to target tumor cells/CSCs, as well as the ability to efficiently generate ROS. This review examines the impact of a smart gold nanoparticle bioconjugate coupled with a photosensitizer (PS) in promoting targeted PDT of cancer and CSC.

Synthesis, optical, structural and biocompatibility assessment of red-emitting CuInS[formula omitted]-ZnS quantum dots conjugated to folic acid

Bioconjugation of nanoparticles is a hot topic of research for a wide range of biological applications, particularly in cancer diagnosis and treatment. In this study, we report the synthesis of glutathione capped CuInS2/ZnS quantum dots (QDs) in an aqueous medium followed by folic acid (FA) modification to produce CIS-ZnS/FA conjugates. The as-synthesized QDs were small, with an average particle diameter of 2.3 nm, and emit in the red region, which was retained even after conjugation with FA. The formation of the conjugates was investigated by ultraviolet–visible (UV–Vis) absorption, photoluminescence (PL) and Fourier transform infrared (FTIR) spectroscopy. The conjugate were then analyzed for their cytotoxicity against both folate receptor (FR) positive (HeLa) and FR negative (A549, C26) cancer cell lines. The results of this study revealed the highly biocompatible nature of the CIS-ZnS/FA conjugates towards both FR positive and negative cancer cell lines and thus they are of potential use in biological applications.

Targeted non AR mediated smart delivery of abiraterone to the prostate cancer.

Prostate cancer is the second-deadliest tumor in men all over the world. Different types of drugs with various delivery systems and pathways were developed, but no one showed prominent results against cancer. Meanwhile, nanoparticles have shown good results against cancer. Therefore, in the given study, citrate mediated synthesized gold nanoparticles (CtGNPs) with immobilized survivin antibodies (SvGNPs) were bioconjugated to the substantially potent drug abiraterone (AbSvGNPs) to develop as a combinatorial therapeutic against prostate cancer. The AbSvGNPs are made up of CtGNPs, survivin antibodies, and abiraterone. The selected drug abiraterone (Abira) possesses exceptionally good activity against prostate cancer, but cancer cells develop resistance against this drug and it also poses several severe side effects. Meanwhile, survivin antibodies were used to deliver AbSvGNPs specifically into cancer cells by considering survivin, an anti-apoptotic overexpressed protein in cancer cells, as a marker. The survivin antibodies have also been used to inhibit cancer cells as an immunotherapeutic agent. Similarly, CtGNPs were discovered to inhibit cancer cell proliferation via several transduction pathways. The given bioconjugated nanoparticles (AbSvGNPs) were found to be substantially effective against prostate cancer with an IC50 of 11.8 and 7.3 μM against DU145 and PC-3 cells, respectively. However, it was found safe against NRK and showed less than 25% cytotoxicity up to 20μM concentration. The as-synthesized nanoparticles CtGNPs, SvGNPs, and AbSvGNPs were characterized by several physical techniques to confirm their synthesis, whereas the immobilization of survivin antibodies and bioconjugation of Abira was confirmed by UV-visible spectroscopy, DLS, TEM, FTIR, and zeta-potential. The anticancer potential of AbSvGNPs was determined by MTT, DAPI, ROS, MITO, TUNEL ASSAY, and caspase-3 activity against DU145 and PC3 cells.

Nanoparticular Carriers As Objects to Study Intentional and Unintentional Bioconjugation.

Synthetic nanoparticles are interesting to use in the study of ligation with natural biorelevant structures. That is because they present an intermediate situation between reactions onto soluble polymers or onto solid surfaces. In addition, differently functionalized nanoparticles can be separated and studied independently thereafter. So what would be a "patchy functionalization" on a macroscopic surface results in differently functionalized nanoparticles, which can be separated after the interaction with body fluids. This paper will review bioconjugation of such nanoparticles with a special focus on recent results concerning the formation of a protein corona by unspecific adsorption (lower lines of TOC), which presents an unintentional bioconjugation, and on new aspects of intentionally performed bioconjugation by covalent chemistry (upper line). For this purpose, it is important that polymeric nanoparticles without a protein corona can be prepared. This opens, e.g., the possibility to look for special proteins adsorbed as a result of the natural compound ligated to the nanoparticle by covalent chemistry, like the Fc part of antibodies. At the same time, the use of highly reactive, bioorthogonal functional groups (inverse electron demand Diels-Alder cycloaddition) on the nanoparticles allows an efficient ligation after administration inside the body, i.e., in vivo.

Detection of SARS-CoV-2 virus via dynamic light scattering using antibody-gold nanoparticle bioconjugates against viral spike protein

Mass testing for the diagnosis of COVID-19 has been hampered in many countries owing to the high cost of genetic material detection. This study reports on a low-cost immunoassay for detecting SARS-CoV-2 within 30 min using dynamic light scattering (DLS). The immunosensor comprises 50-nm gold nanoparticles (AuNPs) functionalized with antibodies against SARS-CoV-2 spike glycoprotein, whose bioconjugation was confirmed using transmission electron microscopy (TEM), UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and surface-enhanced Raman scattering spectroscopy (SERS). The specific binding of the bioconjugates to the spike protein led to an increase in bioconjugate size, with a limit of detection (LOD) 5.29 × 103 TCID50/mL (Tissue Culture Infectious Dose). The immunosensor was also proven to be selective upon interaction with influenza viruses once no increase in size was observed after DLS measurement. The strategy proposed here aimed to use antibodies conjugated to AuNPs as a generic platform that can be extended to other detection principles, enabling technologies for low-cost mass testing for COVID-19.

Bioconjugates of photon-upconversion nanoparticles for cancer biomarker detection and imaging.

The detection of cancer biomarkers in histological samples and blood is of paramount importance for clinical diagnosis. Current methods are limited in terms of sensitivity, hindering early detection of disease. We have overcome the shortcomings of currently available staining and fluorescence labeling methods by taking an integrative approach to establish photon-upconversion nanoparticles (UCNP) as a powerful platform for cancer detection. These nanoparticles are readily synthesized in different sizes to yield efficient and tunable short-wavelength light emission under near-infrared excitation, which eliminates optical background interference of the specimen. Here we present a protocol for the synthesis of UCNPs by high-temperature co-precipitation or seed-mediated growth by thermal decomposition, surface modification by silica or poly(ethylene glycol) that renders the particles resistant to nonspecific binding, and the conjugation of streptavidin or antibodies for biological detection. To detect blood-based biomarkers, we present an upconversion-linked immunosorbent assay for the analog and digital detection of the cancer marker prostate-specific antigen. When applied to immunocytochemistry analysis, UCNPs enable the detection of the breast cancer marker human epidermal growth factor receptor 2 with a signal-to-background ratio 50-fold higher than conventional fluorescent labels. UCNP synthesis takes 4.5 d, the preparation of the antibody-silica-UCNP conjugate takes 3 d, the streptavidin-poly(ethylene glycol)-UCNP conjugate takes 2-3 weeks, upconversion-linked immunosorbent assay takes 2-4 d and immunocytochemistry takes 8-10 h. The procedures can be performed after standard laboratory training in nanomaterials research.

Genistein encapsulated inulin-stearic acid bioconjugate nanoparticles: Formulation development, characterization and anticancer activity

Achieving controlled and site-specific delivery of hydrophobic drugs in the colon environment is a major challenge. The primary goal of this research was to synthesize inulin-stearic acid (INU-SA) conjugate and to evaluate its potential in the site-specific delivery of genistein (GEN) for the treatment of colon cancer. INU is a hydrophilic polysaccharide biological macromolecule was modified with hydrophobic SA to form amphiphilic conjugate (INU-SA) which can self-assemble into spherical nanoparticles with interesting drug release properties. The hydrophobic GEN was encapsulated into the INU-SA conjugate to prepare GEN loaded nanoparticles (GNP). The prepared GNP possessed nano size (115 nm), good colloidal dispersibility (0.066 PDI), and high drug encapsulation efficiency (92.2%). The release behaviour of GNP indicated the site-specific release of GEN, only 3.4% at gastric pH while 94% at intestinal pH. The prepared GNP showed potential cytotoxicity against HCT 116 human colorectal cancer cells, as demonstrated by antiproliferation and apoptosis assays. The observed half maximum inhibitory concentration (IC50) value of GNP (5.5 μg/mL) was significantly lower than pure GEN (28.2 μg/mL) due to higher cellular internalization of GNP than free GEN. Therefore, this research suggests a way to improve the therapeutic effectiveness of natural biomolecules using modified and biocompatible polysaccharide INU.

Biological Impact of the Interaction of Functionalized and Bioconjugated Gold Nanoparticles of Different Sizes on HeLa and SH‐SY5Y Human Cell Lines

Nanotechnology opens new perspectives in many science and technology fields through new materials, such as metal nanoparticles. The biomedical field is one of these areas where nanoparticles offer promising application in the diagnosis and therapy of disease, generating biosensors for disease detection, bioimaging, and drug delivery. However, the controversy about whether nanoparticles are inert or exhibit different degrees of toxicity related to their physicochemical properties remains a subject of study and debate. This work shows how gold nanoparticles and nanorods were simultaneously functionalized with 4‐aminothiophenol (4‐ATP) and methoxypolyethylene glycol thiol (mPEG‐SH). Then, folic acid (FA) gold nanoparticle bioconjugates caused diverse biological effects on HeLa and SH‐SY5Y cell cultures after 24 h of incubation, when they were evaluated in the range of gold concentrations from 0.17 to 350 μM. We found notable changes in cell metabolic activity, viability, and biomass. 16 nm nanoparticles produced the most enhanced damage for functionalized (AuNPs) and bioconjugated (AuNPs‐FA) nanoparticles, which we expected to be more biocompatible when coated with FA. Besides, epifluorescence images showed damage to F‐actin microfilaments, adhesion and cell attachment loss, morphology changes (cells became round and detached), presence of blebs, and rupture of cell membrane. These results suggested that both AuNPs and AuNPs‐FA have significant biological impact on HeLa and SH‐SY5Y cell cultures, whereas gold nanorods showed significant changes only in the metabolic activity of SH‐SY5Y cells when they were exposed to gold nanorods of 23 and 27 nm in length with a diameter of 5 nm, and crystal violet did not show evidence of toxicity.

Synthesis, characterization and biological applications of biofunctional gold nanoparticles for systemic circulation and biological sustainability

Designing nanomaterials for biomedical applications is not a trivial task. Avoidance of the immune system, stability in physiological media, and cell membranes, low toxicity, and optimal bioperformances are critical for the success of the designed nanomaterials. This review focuses on the study of protein-protein and protein-carbohydrates interactions. Most of the biological functions involving biochemical process are closely controlled by protein-protein interactions. Multi-protein complexes perform several catalytic functions. The review also focuses on the in vitro synthesis of bioconjugated nanoparticles and their biological applications such as antimicrobial agents and drug delivery vehicles. The synthesized nanoparticles act as sensor for such interactions. The in vitro synthesis of Au NPs also helps to understand such interactions with better clarity, which are otherwise elusive in the absence of NPs due to their highly complex nature. Both lysozyme (Lys) / Cytochrome, c (Cyt. c) and lysozyme/zein complexes showed remarkable surface adsorption on NP surfaces. The former system produced pH responsive NPs due to its amphiphilic nature and good antimicrobial properties while the latter system produced pH insensitive NPs due to its hydrophobic nature dominated by zein due to presence of non-polar amino acids such as leucine, alanine and proline. Due to insignificant hemolysis both systems may be used as drug delivery vehicles in systemic circulation. The diethylaminoethyl dextran chloride (DEAE) -protein interactions showed that DEAE-BSA and DEAE-Lys mixtures are amphiphilic whereas DEAE-zein mixture is hydrophobic in nature. All different complexes demonstrate strong surface adsorption on both presynthesized Au NPs as well as in vitro synthesis of Au NPs, which leads to the formation of biofunctional Au NPs best suited for biological applications in systemic circulation. The biological applicability is demonstrated from the hemolysis measurements where both DEAE−BSA as well as DEAE−Lys coated Au NPs do not show any marked hemolysis, thus proving to be the best suited vehicles for drug release in systemic circulation. DEAE−zein coated NPs, on the other hand, showed this behavior only in the DEAE rich region of the mixture, but in the protein rich region hemolysis dominates. Copyright © 2017 VBRI Press.