Synthesis Of Nanogels Research Articles

Dual Temperature and pH Sensitive Poly(ethyl methacrylate‐co‐acrylamide) Nanogels Have Potential for Controlled Release of Doxorubicin

AbstractIn this study, the synthesis and characterization of poly(ethyl methacrylate‐co‐acrylamide) (i.e., poly(EMA‐co‐AAm)) nanogels and the loading and release studies of doxorubicin hydrochloride were carried out. The synthesis of nanogels was carried out using the emulsion polymerization technique at 60 °C. Swelling experiments showed that the nanogels were sensitive to temperature and pH of the medium. Zeta sizer analysis results showed that the synthesized nanogels had an average size of 23.17 nm and the PDI value was 0.270. In the loading studies of doxorubicin into nanogels, the drug loading capacity (DLC) of the nanogel was determined as 32% and the drug loading efficiency (DLE) was determined as 77%. Release studies conducted at pH = 5.4 and pH = 7.4 at 37 °C showed that the release percentage was 17% even in 32 h at pH = 7.4, and 82% in 5 h at pH = 5.4. Release studies conducted at different temperatures at pH = 5.4 revealed that the release percentage was 82% at 37 °C, 85% at 39 °C, and 89% at 41 °C. These results revealed that poly(EMA‐co‐AAm) nanogels can be used in targeted controlled release of doxorubicin and can increase drug effects while reducing side effects.

Influencing Factors and Stimulus-Sensitivity of Chitosan/Polymethacrylic Acid (CS/PMAA) Nanogels as Nanocarriers

ABSTRACT Nanogel, nanosized hydrogel, can contribute to biomedical and pharmaceutical, especially in drug delivery, due to its enthralling properties. Small size, large surface area, hydrophilicity, and stimulus responsiveness of nanogel ameliorate tissue penetration, drug loading capacity, and targeted drug delivery. The current study prepared nanosized, pH-sensitive, biocompatible, and stable chitosan/polymethacrylic acid (CS/PMAA) based nanogels using MBA as a crosslinker and APS as an initiator. FTIR confirmed the reaction between functional groups to synthesize nanogels sufficiently in a spherical shape, as affirmed by a FESEM. DLS data revealed nanosized particles with a size range of 70–170 nm and a range of 6–13 for polydispersity index (PDI). A study showed that 2% of MBA crosslinker is sufficient to achieve the desired crosslinking in 60 minutes reaction time (RT) with nanogel size ~ 92 nm. Increasing RT from 30 to 80 minutes during nanogel synthesis demonstrated a decrease in nanogel sizes from 186–73 nm. Synthesized nanogels have shown pH sensitivity (stimuli responsiveness) in acidic and alkaline mediums with an increase in particle size in pH-2 (~144 nm) and pH-8 (~280 nm) compared to intermediate pHs. The pH sensitivity of nanogels by changing the size per the suspended medium’s pH is crucial for prolonged systemic circulation and targeted drug delivery. Moreover, nanogels have shown good colloidal stability with zeta potential (ZP) +28 mv in acidic and −38 mv alkaline mediums. DSC and XRD results demonstrated thermal stability and amorphous morphology of nanogels, respectively. BET surface analysis revealed the surface area of nanogels in the range of 65–68 cm2/g with an average pore size of 28–32 nm. In-vitro cytotoxicity in the L-929 cell line by MTT assay established the cell viability (>70%) after 24 hours of incubation, substantiating the non-toxicity and biocompatibility of nanogels as nanocarriers for drug delivery.

Controlled polymerization in microfluidics: Advancement in nanogel synthesis

AbstractThis comprehensive review provides a detailed examination of controlled polymerization in the development of nanogels‐based microfluidic devices. Here, we have explored the integration of atom transfer radical polymerization (ATRP) and reversible addition‐fragmentation chain transfer (RAFT) techniques within microfluidic platforms for the synthesis of nanogels. The synergistic combination of ATRP and RAFT with microfluidics has emerged as a powerful tool for precise control over polymerization reactions, enabling the fabrication of well‐defined, multifunctional nanogels with tailored properties. The review begins with a thorough introduction to the principles of ATRP and RAFT, highlighting their respective advantages in controlled radical polymerization. Subsequently, it elucidates the principles of microfluidics and its profound impact on polymerization processes. The merging of these techniques enables precise control over reaction kinetics, monomer conversions, and molecular weight distributions, facilitating the synthesis of nanogels with unprecedented precision and reproducibility. Furthermore, this review delves into the chemical mechanisms underlying ATRP and RAFT reactions in microfluidic environments, emphasizing the role of various initiators, catalysts, and chain transfer agents. Special attention is given to the impact of microscale flow conditions on reaction kinetics and polymer structure. In addition, the review discusses emerging trends in the field, such as the incorporation of novel monomers and the exploration of environmentally benign reaction conditions.Highlights The controlled polymerization is the mechanism by which we can obtain tailormade material. The nanogel synthesis must ensure the gelation to be in confined dimensions here microfluidics plays key role.

Herbal nanogels: Revolutionizing skin cancer therapy through nanotechnology and natural remedies

The escalating global incidence of skin cancer demands innovative therapeutic approaches that balance efficacy and reduced side effects. The convergence of nanotechnology and medicinal research has unveiled herbal nanogels as promising candidates for advancing skin cancer therapy. Skin cancer, comprising diverse malignancies, necessitates novel strategies to enhance treatment outcomes. Nanogels, intricate networks of cross-linked polymers at the nanoscale, have emerged as versatile vehicles for targeted drug delivery. Their ability to encapsulate a range of therapeutic agents and respond to stimuli offers a platform to revolutionize treatment paradigms. The taxonomy of nanogels encompasses physical cross-linked gels, liposome-modified nanogels, micellar nanogels, hybrid nanogels, and chemically cross-linked nanogels, each holding distinctive characteristics suitable for specific applications. The synthesis of nanogels is a precise craft involving techniques like photolithography, micro-moulding, and emulsion methods, enabling control over particle size, morphology, and drug-loading capacity. Stimuli-responsive nanogels present a dynamic facet of this field, exhibiting potential for targeted drug delivery. Noteworthy examples include LHRH-targeted nanogels and nanogels responsive to the intricate microenvironment of bacterial-accumulated tumors. One of the most intriguing developments lies in the fusion of herbal medicine and nanotechnology, paving the way for herbal nanogels. By incorporating bioactive plant-derived compounds into nanogel matrices, these constructs offer a holistic therapeutic approach. The convergence of nanotechnology and herbal medicine in the form of herbal nanogels presents a promising avenue for elevating skin cancer therapy. Through precise drug delivery mechanisms and responsiveness to complex microenvironments, nanogels exhibit a potential to reshape treatment norms. This comprehensive review provides an in-depth roadmap of the evolving landscape of herbal nanogels, illuminating their potential as effective, targeted, and minimally invasive tools for combating skin cancer.

Design of Nanohydrogels for Targeted Intracellular Drug Transport to the Trans-Golgi Network.

Nanohydrogels combine advantages of hydrogels and nanoparticles. In particular, they represent promising drug delivery systems. Nanogel synthesis by oxidative condensation of polyglycidol prepolymers, that are modified with thiol groups, results in crosslinking by disulfide bonds. Hereby, biomolecules like the antidiabetic peptide RS1-reg, derived from the regulatory protein RS1 of the Na+ -D-glucose cotransporter SGLT1, can be covalently bound by cysteine residues to the nanogel in a hydrophilic, stabilizing environment. After oral uptake, the acid-stable nanogels protect their loading during gastric passage from proteolytic degradation. Under alkaline conditions in small intestine the nanohydrogels become mucoadhesive, pass the intestinal mucosa and are taken up into small intestinal enterocytes by endocytosis. Using Caco-2 cells as amodel for small intestinal enterocytes, by confocal laser scanning microscopy and structured illumination microscopy, the colocalization of fluorescent-labeled RS1-reg with markers of endosomes, lysosomes, and trans-Golgi-network after uptake with polyglycidol-based nanogels formed by precipitation polymerization is demonstrated. This indicates that RS1-reg follows the endosomal pathway. In the following, the design of bespoken nanohydrogels for specific targeting of RS1-reg to its site of action at the trans-Golgi network is described that might also represent a way of targeted transport for other drugs to their targets at the Golgi apparatus.

Nanogel-based scaffolds for tissue engineering and regenerative medicine

Nanogels are an emerging class of nanomaterials that have shown great potential for biomedical applications, particularly in the field of tissue engineering and regenerative medicine. Nanogel-based scaffolds are promising due to their unique properties, such as high water content, biocompatibility, and tunable drug release. This review article provides an overview of the current state-of-the-art in nanogel-based scaffolds, including their synthesis and characterization, properties, applications in tissue engineering and regenerative medicine, challenges and limitations, and future directions. The synthesis of nanogels is discussed, along with the various methods used for their characterization, such as size and zeta potential measurements, microscopy, and spectroscopy. The unique properties of nanogel-based scaffolds, such as their high water content and tunable drug release, are also discussed in detail. The review article highlights the applications of nanogel-based scaffolds in tissue engineering and regenerative medicine, including their use in wound healing, bone regeneration, and drug delivery. Additionally, the challenges and limitations of nanogel-based scaffolds are discussed, along with future directions for research in this exciting field. Overall, this review article provides a comprehensive overview of the current state-of-the-art in nanogel-based scaffolds, highlighting their potential for future biomedical applications.

Nanogel for Selective Recognition of Nanoparticles in Water Samples

Nanoparticles (NPs) represent emerging pollutants that still pose analytical challenges for their detection in environmentally relevant samples due to their extremely low concentrations, high colloidal background, and the need to perform speciation analysis. They are also one of the interfering matrices during the analysis of metal ions and contaminants in water samples. Currently, conventional analytical techniques such as Transmission Electron Microscopy (TEM) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) are used for the detection of NPs, but such techniques require bulky instrumentation and are difficult to be automated for online analysis. In this study, we aim to develop a nanoparticle-imprinted hydrogel (NPIH, NANOGEL) to detect and capture NPs in water samples. The principle of the Nanogel originates from the well-known concept of molecularly imprinted polymers (MIPs). Cadmium sulfide/Selenide/Zinc sulfide core/shell quantum dots (QDs) were used as the template NP, creating specific pore cavities in the Nanogel that can selectively bind to certain analytes. Quantification of NPs detected in water samples was then made possible by transducing this selective detection process into an analytical signal using a quartz crystal microbalance (QCM). The Nanogel was shown to demonstrate good repeatability, reproducibility, and stability in terms of its performance. The high selectivity of the Nanogel was determined to be attributed to the size of cavities and their surface characteristics. Ionic interference was present and, heavy metal cations showed an affinity for the NANOGEL synthesized; however, they were demonstrated to be minimized by the selection of porogenic solvents during the synthesis of NANOGEL. We believe that the Nanogel would provide a highly selective and sensitive approach for the detection of NPs in aqueous samples and the removal of NPs from contaminated water resources. It will serve useful in environmental applications.

CuAAC ensembled 1,2,3-triazole linked nanogels for targeted drug delivery: a review.

Copper(i) catalyzed alkyne azide cycloaddition (CuAAC), the quintessential example of 'click chemistry', provides an adaptable and adequate platform for the synthesis of nanogels for sustained drug release at targeted sites because of their better biocompatibility. The coupling of drugs, carried out via various synthetic routes including CuAAC, into long-chain polymeric forms like nanogels has exhibited considerable assurance in therapeutic advancements and intracellular drug delivery due to the progression of water solubility, evacuation of precocious drug release, and improved upthrust of the pharmacokinetics of the nanogels, thereby rendering them as better and efficient drug carriers. The inefficiency of drug transmission to the target areas due to the resistance of complex biological barriers in vivo is a major hurdle that impedes the therapeutic translation of nanogels. This review compiles the data of nanogels synthesized specifically via CuAAC 'click' methodology, as scaffolds for targeted drug delivery and their assimilation into nanomedicine. In addition, it elaborates the ability of CuAAC to graft specific moieties and conjugating biomolecules like proteins and growth factors, onto orthogonally functionalized polymer chains with various chemical groups resulting in nanogels that are not only more appealing but also more effective at delivering drugs, thereby enhancing their site-specific target approach and initiating selective therapies.

Polyvinylpyrrolidone K-30-Based Crosslinked Fast Swelling Nanogels: An Impeccable Approach for Drug's Solubility Improvement.

Poor solubility is a global issue of copious pharmaceutical industries as large number of drugs in development stage as well as already marketed products are poorly soluble which results in low dissolution and ultimately dosage increase. Current study is aimed at developing a polyvinylpyrrolidone- (PVP-K30-) based nanogel delivery system for solubility enhancement of poorly soluble drug olanzapine (OLP), as solubilization enhancement is the most noteworthy application of nanosystems. Crosslinking polymerization with subsequent condensation technique was used for the synthesis of nanogels, a highly responsive polymeric networks in drug's solubility. Developed nanogels were characterized by percent entrapment efficiency, sol-gel, percent swelling, percent drug loaded content (%DLC), percent porosity, stability, solubility, in vitro dissolution studies, FTIR, XRD, and SEM analysis. Furthermore, cytotoxicity study was conducted on rabbits to check the biocompatibility of the system. Particle size of nanogels was found with 178.99 ± 15.32 nm, and in vitro dissolution study exhibited that drug release properties were considerably enhanced as compared to the marketed formulation OLANZIA. The solubility studies indicated that solubility of OLP was noticeably improved up to 36.7-fold in phosphate buffer of pH 6.8. In vivo cytotoxicity study indicated that prepared PVP-K30-based formulation was biocompatible. On the basis of results obtained, the developed PVP-K30-co-poly (AMPS) nanogel delivery system is expected to be safe, effective, and cost-effective for solubility improvement of poorly soluble drugs.

Valorization of lignin into nanoparticles and nanogel: Characterization and application

A simple, time efficient process for valorization of lignin into lignin nanoparticles (LNPs) and further into nanogels was developed. LNPs were morphologically spherical with average size of ~136 nm as observed through SEM and particle size analysis. LNPs were applied for nanogel synthesis through UV-curing process in indigenously designed and developed curing cabinet by incorporating them into acrylamide, bis-acrylamide and 1-hydroxycyclohexyl phenyl ketone acting as monomer, cross-linker and photoinitiator, respectively. Nanogels were characterized through SEM, FTIR and compared with hydrogel (gel without LNPs). Mechanical properties of nanogel were analyzed through compression test. Nanogel was found to have better load bearing capacity and Young's modulus (0.8 kPa), which was 4× higher than hydrogel (0.2 kPa). Further, nanogel was used for water retention application and showed 1.6 times higher water retention capacity as compared to hydrogel. Developed nanogel has suitable application in drought prone areas due to its water retention capacity.

Droplet-based microfluidic synthesis of nanogels for controlled drug delivery: tailoring nanomaterial properties via pneumatically actuated flow-focusing junction

Conventional batch syntheses of polymer-based nanoparticles show considerable shortcomings in terms of scarce control over nanomaterials morphology and limited lot-to-lot reproducibility. Droplet-based microfluidics represents a valuable strategy to overcome these constraints, exploiting the formation of nanoparticles within discrete microdroplets. In this work, we synthesized nanogels (NGs) composed of hyaluronic acid and polyethyleneimine using a microfluidic flow-focusing device endowed with a pressure-driven micro-actuator. The actuator achieves real-time modulation of the junction orifice width, thereby regulating the microdroplet diameter and, as a result, the NG size. Acting on process parameters, NG hydrodynamic diameter could be tuned in the range 92-190 nm while preserving an extremely low polydispersity (0.015); those values are hardly achievable in batch syntheses and underline the strength of our toolbox for the continuous in-flow synthesis of nanocarriers. Furthermore, NGs were validated in vitro as a drug delivery system in a representative case study still lacking an effective therapeutic treatment: ovarian cancer. Using doxorubicin as a chemotherapeutic agent, we show that NG-mediated release of the drug results in an enhanced antiblastic effect vs. the non-encapsulated administration route even at sublethal dosages, highlighting the wide applicability of our microfluidics-enabled nanomaterials in healthcare scenarios.

On the Mechanism and Kinetics of Synthesizing Polymer Nanogels by Ionizing Radiation-Induced Intramolecular Crosslinking of Macromolecules.

Nanogels—internally crosslinked macromolecules—have a growing palette of potential applications, including as drug, gene or radioisotope nanocarriers and as in vivo signaling molecules in modern diagnostics and therapy. This has triggered considerable interest in developing new methods for their synthesis. The procedure based on intramolecular crosslinking of polymer radicals generated by pulses of ionizing radiation has many advantages. The substrates needed are usually simple biocompatible polymers and water. This eliminates the use of monomers, chemical crosslinking agents, initiators, surfactants, etc., thus limiting potential problems with the biocompatibility of products. This review summarizes the basics of this method, providing background information on relevant aspects of polymer solution thermodynamics, radiolysis of aqueous solutions, generation and reactions of polymer radicals, and the non-trivial kinetics and mechanism of crosslinking, focusing on the main factors influencing the outcomes of the radiation synthesis of nanogels: molecular weight of the starting polymer, its concentration, irradiation mode, absorbed dose of ionizing radiation and temperature. The most important techniques used to perform the synthesis, to study the kinetics and mechanism of the involved reactions, and to assess the physicochemical properties of the formed nanogels are presented. Two select important cases, the synthesis of nanogels based on polyvinylpyrrolidone (PVP) and/or poly(acrylic acid) (PAA), are discussed in more detail. Examples of recent application studies on radiation-synthesized PVP and PAA nanogels in transporting drugs across the blood–brain barrier and as targeted radioisotope carriers in nanoradiotherapy are briefly described.

Overview of nanogel and its applications

Nanogel have emerged as a versatile drug delivery system for encapsulation of guest molecules. A nanoparticle which is composed of hydrophilic polymer network known as Nanogel having range from 100-200nm. Nanogel have swellable and degradation properties with high drug loading capacity, high stability, sustained and targetable manner, large surface area. Therefore, nanogel are more productive than conventional and micro-sized delivery. In recent year in the field of biotechnology nanogel were prominently used to deal with genetics, enzyme immobilization and protein synthesis. Moreover, it has productive asset for the development of novel therapeutic system in medicine. These are soft materials capable of holding small molecular biomacromolecules, therapeutics, and inorganic nanoparticles within their crosslinked networks, which allows them to find applications for therapy as well as imaging of a variety of disease conditions. These properties not only enhance the functionality of the carrier system but also help in overcoming many challenges associated with the delivery of cargo molecules. This review aims to highlight the distinct and unique capabilities of nanogels as carrier system, Synthesis of nanogels, Types of Physical and chemical crosslinked nanogels, Stimuli responsive behavior, In vivo behavior, Therapeutic drug carrier, marketed formulation of Nanogels and the last part of review summarizes the applications of nanogels in various diseases. Transdermal drug delivery, diabetes, anti-inflammatory, vaginal drug delivery, neurodegenerative diseases, ocular dieses, autoimmune disease, and anticancer treatment for specially targeting the cancer cells, thereby reducing uptake into healthy cells. This nanogel drug delivery is a phenomenal system, and further depth study is required to explore their interaction at cellular and molecular levels and minimize the challenges.

Improved Solvothermal Synthesis of γ-Fe2O3 Magnetic Nanoparticles for SiO2 Coating.

Monodisperse magnetic γ-Fe2O3 nanoparticles (MNPs) were prepared by a simple, improved, one-pot solvothermal synthesis using SDS and PEG 6000 as double capping reagents. This double protecting layer afforded better MNP uniformity (Z average 257 ± 11.12 nm, PDI = 0.18) and colloidal stability. Materials were characterized by DLS, SEM, TEM, XPS, and XRD. The use of these MNPs in the synthesis of core–shell structures with uniform and tunable silica coatings was demonstrated, as silica coated MNPs are important for use in a range of applications, including magnetic separation and catalysis and as platforms for templated nanogel synthesis.

Synthesis of pH-sensitive hyaluronic acid nanogels loaded with paclitaxel and interferon gamma: Characterization and effect on the A549 lung carcinoma cell line

Lung cancer is one of the deadliest cancers in various populations. Apart from the effects that anticancer drugs such as paclitaxel (PTX) have on cancer cells, they also have many side effects on healthy cells. Interferon gamma (IFN-γ) is also one of the cytokines used in the treatment of cancer. Current research is focused on providing new drug carriers to find new therapeutic goals. After synthesis of nanogels and loading of PTX and IFN-γ, the cytotoxicity of these nanogels on A549 and HEK293 healthy cell line was measured by MTT assay and flow cytometry analysis. Finally, the expression of STAT1 gene was investigated using Real time-PCR. The results of MTT assay showed that the survival rate of healthy cells treated with PTX and IFN-γ-loaded nanogels was 2.15 and 2.39 times higher than cancer cells, respectively. The results also showed that the gene expression STAT1 in A549 cells exposed to these nanogels was higher than healthy cells (p < 0.05). Based on flow cytometry results, the death rate of healthy cells treated with the mentioned nanogels was lower than cancer cells (p < 0.05). Therefore, Studies showed that synthesized nanogels have positive effects on cancer cells and also have fewer side effects on healthy cells.

A Sampling of Highlights from the Literature: Article Recommendations from Our Deputy and Senior Editors.

A two-step circuit allows ultrasensitive sensing of antigen density (from Ron Mader via Flickr)Recognition of normal cells expressing a low density of target antigen is a barrier to chimeric antigen receptor (CAR) T–cell therapy for some cancers. Hernandez-Lopez et al. have designed a two-step antigen-recognition circuit enabling CAR T cells to distinguish cells expressing high and low densities of target antigen. They engineer T cells to express a synthetic Notch receptor with low affinity for HER2. HER2 recognition by this receptor drives expression of a CAR with high affinity for HER2. These cells kill tumor cell lines and 3D spheroids expressing high densities of HER2 but spare those with low densities of HER2, showing this approach could limit on-target, off-tumor responses.Hernandez-Lopez RA, …, Lim WA. Science 2021 Mar 12;371:1166–71.Alveolar rhabdomyosarcoma (from Nephron via Wikimedia Commons)Increased understanding of the microenvironment at distant sites prior to metastases becoming detectable at those sites could lead to new strategies for treating metastases. In a syngeneic orthotopic model of rhabdomyosarcoma that spontaneously metastasizes to the lungs, Kaczanowska et al. identify a transcriptional program indicative of myeloid-mediated immune suppression in the premetastatic lung. Intravenous administration of myeloid cells genetically engineered to express IL12 reprograms the premetastatic niche, reversing the immunosuppressive phenotype and inducing T cell–mediated antitumor immunity, such that metastases are reduced and survival improved. These data suggest a new strategy for treating metastatic disease.Kaczanowska S,…, Kaplan RN. Cell 2021 Apr 15;184:2033–52.e21.MRTFs play dual roles in cancer and antitumor immunity (from Fig. 1 of Finch-Edmondson et al., Cell Mol Biol Lett 2016)Tumor cells have multiple ways of evading immune detection. Tello-Lafoz et al. find that myocardin-related transcription factors (MRTF) are “double agents.” On one hand, MRTFs support tumor progression and metastasis, but on the other hand, high expression boosts CTL and natural killer–cell activation, an effect enhanced by anti-CTLA4 therapy. High MRTF expression also alters the rigidity of the tumor cell F-actin cytoskeleton, a mechanical change that renders the tumor cells more susceptible to elimination. The data bring to light “mechanical” changes that can occur that allow for improved immunosurveillance and tumor killing.Tello-Lafoz M, …, Er EE. Immunity 2021 Mar 22. DOI: 10.1016/j.immuni.2021.02.020.CD161 on T cells is inhibitory (T/NK-cell CD161 IHC; from Fig. 2F of Dorfeshan et al., Biomed Res Int 2013)T cells play a vital role in the efficacy of immunotherapies. Using single-cell RNA sequencing, Mathewson et al. analyze tumor-infiltrating T cells in patients with glioma. They identify clonal CD8+ T cells coexpressing cytotoxic programs and natural killer (NK) cell–associated genes, including CD161 (encoded by KLRB1). CD161 is identified as an inhibitory receptor that limits T cell–mediated tumor killing. Inactivation of KLRB1 or blockade of CD161 restores T-cell killing of glioma targets in vitro and in vivo. These data point to CD161 and other NK cell–associated receptors (expressed by T cells) as potential immunotherapeutic targets.Mathewson ND, …, Wucherpfennig KW. Cell 2021 Mar 4;184:1281–98.e26.Bacteria-derived peptides can be presented by tumor cells (by Moustafa Abdou via Ask Hematologist/Understand Hematology)Bacteria are associated with some cancers and have a role in modulating immune function. Kalaora et al. investigate whether bacterial antigens are expressed on melanoma HLA molecules. More than 250 bacteria-derived peptides, originating from 41 bacterial species, are identified. A subset of these peptides are not only presented by HLA-I/II in different tumors within the same patient but also found across samples from different patients. The peptides presented by tumor cells are immunogenic and activate tumor-infiltrating lymphocytes ex vivo, providing further insight into the impact of bacteria on antitumor immunity.Kalaora S, …, Samuels Y. Nature 2021 Apr 1;592:138–43.3-D rendering of a neutrophil (from Blausen.com staff via Wikimedia Commons)Microrobots controlled by rotating magnetic fields have potential to allow precise therapeutic targeting of cancers. However, current microrobots are susceptible to immune clearance and cannot efficiently penetrate biological barriers such as the blood–brain barrier. Zhang et al. show these challenges can be addressed using neutrophil-based microrobots, referred to as “neutrobots.” Neutrobots are made in three steps: first, synthesis of nanogels loaded with hydrophobic Fe3O4 nanoparticles and paclitaxel; second, coating of the nanogels with the outer membrane of Escherichia coli; and third, phagocytosis of the coated nanogels by neutrophils. The neutrobots accurately deliver paclitaxel in a postoperative orthotopic glioma model, increasing survival, thereby highlighting the therapeutic potential of neutrobots.Zhang H, …, He Q. Science Robotics 2021 Mar 24;6:eaaz9519.

Optimal synthesis of polyelectrolyte nanogels by electrostatic assembly directed polymerization for dye loading and release.

Polyelectrolyte (PE) nanogels which combine features of nanogels and polyelectrolytes have attracted significant attention as outstanding nano-carriers. However, and crucially, any large-scale application of PE nanogels can only materialize when an efficient production method is available. We recently developed such a robust approach, namely Electrostatic Assembly Directed Polymerization (EADP), in which ionic monomers are polymerized together with cross-linker in the presence of a polyion-neutral diblock copolymer as template. Although EADP achieves efficient and scalable preparation of diverse PE nanogels, the essential factors for the optimal and controlled synthesis of nanogels have remained elusive. In this article, we investigate systematically the effects of pH, salt concentration, and cross-linker fractions on the formation and properties of a PDMAEMA nanogel prepared with PAA-b-PEO as the template. We find that the electrostatic interaction between the building blocks is crucial to obtain assembly-controlled polymerization, and we establish preferred pH, salt concentration and cross-linker fractions. The obtained PDMAEMA nanogel exhibits dual-responses to pH and salt, which allow manipulation of the positive charges of the nanogels for selective loading and controlled release of anionic substances; we demonstrate this with an anionic dye. The study presented here fully addresses the process parameters of EADP regarding optimal and controlled preparation of PE nanogels, which should allow exploration of their potential vis-a-vis a variety of applications.

Simultaneous Cross-Linking and Cross-Polymerization of Enzyme Responsive Polyethylene Glycol Nanogels in Confined Aqueous Droplets for Reduction of Low-Density Lipoprotein Oxidation.

A key initiating step in atherosclerosis is the accumulation and retention of apolipoprotein B complexing lipoproteins within the artery walls. In this work, we address this exact initiating mechanism of atherosclerosis, which results from the oxidation of low-density lipoproteins (oxLDL) using therapeutic nanogels. We present the development of biocompatible polyethylene glycol (PEG) cross-linked nanogels formed from a single simultaneous cross-linking and co-polymerization step in water without the requirement for an organic solvent, high temperature, or shear stress. The nanogel synthesis also incorporates in situ noncovalent electrostatically driven template polymerization around an innate anti-inflammatory and anti-oxidizing paraoxonase-1 (PON-1) enzyme payload-the release of which is triggered because of matrix metalloproteinase responsive elements instilled in the PEG cross-linker monomer. The results obtained demonstrate the potential of triggered release of the PON-1 enzyme and its efficacy against the production of ox-LDL, and therefore a reduction in macrophage foam cell and reactive oxygen species formation.

Synthesis and characterization of dihydrocaffeic acid grafted chitosan nanogel for nanoencapsulation of Matricaria recutita essential oil

In this work, we report the synthesis of a nanogel of chitosan bound to dihydrocaffeic acid (CS-DHCA) to be applied in the encapsulation of the essential oil of Matricaria recutita, to enable its use as an antioxidant. The results of ATR-FTIR and 13C SSNMR analysis showed that the nanogel synthesis was efficient. In an aqueous medium, the nanogel showed stability and an average particle size of 206.6 ± 65.1 nm. The material obtained presented an encapsulation capacity of 61.23% of the essential oil. The SEM analyses demonstrated the presence of essential oil inside the nanogel. The nanogel containing encapsulated essential oil showed a higher antioxidant capacity by the ABTS assays (109.42 ± 5.91 μM trolox/g nanogel) and FRAP (264.64 ± 3.57 mM of ferrous sulfate/g nanogel). With the synthesis of this nanogel, CS-DHCA was able to obtain a material capable of improving the applicability of M. recutita essential oil as an antioxidant.

The effect of water/ethanol ratio and monomer concentration on the size and morphology of polyacrylamide nanogels in a surfactant-free synthesis

In this contribution, we propose a polyacrylamide surfactant-free nanogel synthesis technique in a water/ethanol system using N,N'-methylenebisacrylamide (MBAm) as a crosslinker agent. The polymerization reactions were carried out using the potassium persulfate (KPS) and N,N,N′,N′-tetramethylethylenediamine (TEMED) redox pair. The main contribution of this paper is a two-dimensional study of the particle size, polydispersity, and morphology as a function of the solvent water/ethanol wt. ratio and wt. % of monomer (acrylamide, AM) during the particle synthesis. The results show that the obtained particles have a similar morphology compared to those prepared using surfactants. The particle size was measured using Quasi-Elastic Light Scattering (QELS) of the redispersed nanogel, obtaining particle sizes from 41 to 1050 nm, with polydispersity values between 0.31 and 1. In all cases, we found three particle sizes with different abundance distributions, each having a prevailing abundancy ranging from 65% to 95%. Finally, the nanogel morphology was analyzed with Field Emission Scanning Electron Microscopy (FE-SEM) and Transmission Electron Microscopy (TEM).