Biomimetic LHRH-functionalized erythrocyte-camouflaged nanogels for targeted therapy of prostate cancer.

Objective: To evaluate the clinical efficacy, bacterial control ability, and the molecular mechanisms underlying the wound healing effects of Berberin nano gel compared with Silver Sulfadiazine 1% cream (SSD 1%) on superficial thermal burns in pediatric patients. Methods: A prospective, controlled, within-patient (split-wound) study in 34 children with II-III degree burns treated at Le Huu Trac National Burn Hospital. Each child had two damaged zones that were equivalent: Zone A was treated with Berberine nano gel, and Zone B was treated with SSD 1%. Evaluation of complete healing time, time to 50% epithelialization, surface bacterial load (D0, D7, D14), and CHEOPS pain score. Results: Time to complete healing was shortened with Berberine nano gel: superficial second-degree 8.26 ± 2.45 days vs. 9.71 ± 2.95 days; third-degree 14.85 ± 5.20 days vs. 18.41 ± 6.56 days (p <0.05). The bacterial load was reduced in both zones over time. At D7, it was significantly lower in the Berberine nano gel group (43.22 ± 37.28 vs. 92.59 ± 81.14 CFU units; p <0.05), whereas at D14 the difference was not significant. The drug was well tolerated, with a mean CHEOPS of 1.56 ± 1.56. Conclusion: Berberine nano gel shortens wound healing time, improves early bacterial control, and is a potential alternative to 1% SSD for the treatment of superficial burns in children.

Objective: To evaluate the In vitro antibacterial activity of berberine nanogel against reference bacterial strains and compare it with a reference control.Subjects and methods: In vitro experimental design. Antibacterial activity was quantified using the agar disk diffusion method (zone of inhibition, mm). Time-kill assays were conducted using twofold serial dilutions (from 1/2 to 1/128) with with bacterial growth assessed at 2, 6, and 24 hours for Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.Results: The berberine nanogel produced zones of inhibition against both Gram-positive and some Gram-negative bacteria. Specifically: E. coli 17.11 ± 1.44 mm vs. the reference control 23.49 ± 2.16 mm (p < 0.001); P. aeruginosa 14.14 ± 1.61 mm vs. 14.25 ± 1.88 mm (p > 0.05); Acinetobacter sp. 19.79 ± 1.37 mm vs. 10.59 ± 1.19 mm (p < 0.001); Enterobacter sp. 15.26 ± 1.58 mm vs. 24.26 ± 0.97 mm (p < 0.001). For Gram-positive bacteria, S. aureus achieved 16.47 ± 1.54 mm vs. 11.20 ± 1.37 mm (p < 0.001). In time - kill testing, no bacterial growth was observed after 24 hours at dilutions ≥1/16 for E. coli and P. aeruginosa, and at ≥ 1/32 for S. aureus. At higher concentrations (≥1/4), early inhibition/bactericidal activity was evident as early as 2 hours.Conclusion: Berberine nanogel demonstrated significant In vitro antibacterial activity, with pronounced effects against S. aureus and Acinetobacter sp., and efficacy comparable to the reference control against P. aeruginosa.

Peptide-based nanogels (NGs) represent a cutting-edge class of nanoscale drug delivery systems. Due to their structural properties, NGs platforms can encapsulate and protect therapeutic agents (e.g. peptides, proteins, and nucleic acids), while allowing for controlled and stimuli-responsive release. These pharmacokinetic and pharmacodynamic features can be specifically tuned by including peptide functional elements as NG components. This study explores the formulation, decoration strategies, and structural properties of NGs derived from mixed hydrogel (HG) matrices of Fmoc-diphenylalanine (Fmoc-FF) with cationic amphiphilic peptides (CAPs). CAPs, composed by cationic hexapeptide (GK)3 sequence decorated at its N-terminus with alkyl chain, were found able to confer a net positive charge to Fmoc-FF NGs. Fmoc-FF/C16-(GK)3 and Fmoc-FF/C18-(GK)3 NGs were obtained using polysorbate 80 (TWEEN 80) and sorbitane monooleate 80 (SPAN 80) as colloidal stabilizing surfactants and characterized in terms of size, secondary structure, superficial charge and shelf stability by Dynamic Light Scattering (DLS), Circular Dichroism (CD), Fourier Transform Infrared (FT-IR) and Small-Angle X-ray Scattering (SAXS) technique. Different formulative routes were used and mutually compared to encapsulate or adsorb AlexaFluor 430 (succinimidyl ester), used as model of an anionic, pharmaceutical agent. In vitro experiments demonstrated good cytocompatibility of these systems and the release of AlexaFluor 430 was also evaluated.

Adsorption and nanoencapsulation: Innovative strategies for recovery and protection of flavonoids from Malpighia emarginata DC. (acerola) pomace extract.

Background/Objectives: Nanogels (NGs) are promising carriers for drug delivery due to their tunable size, biocompatibility, and capability to encapsulate sensitive molecules. However, conventional batch synthesis often lacks control over key parameters, such as size distribution and encapsulation efficiency. This study aimed to develop a microfluidic platform for the reproducible synthesis of poly(α-glutamic acid) (PGA)-based NGs using strain-promoted azide–alkyne cycloaddition (SPAAC) click chemistry and to investigate the effects of flow parameters on the physicochemical properties of nanogels. Methods: Functionalized PGAs (with azide and DBCO) were co-injected into a microfluidic system within a flux of acetone to form NGs via SPAAC. Flow rate ratios (FRR) and total flow rates were systematically screened at 25 °C, with tests at 50 °C. We evaluated the particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency (EE%) of doxorubicin-loaded NGs. Results: NGs with tunable sizes ranging from ~50 nm to >170 nm and low PDI (<0.1 in optimal conditions) were obtained. Higher FRR and total flow rates yielded smaller and more uniform NGs. Doxorubicin loading did not affect the nanogel size and uniformity, and in some cases, it improved them. The EE% reached up to ~65%, and ~40% for the best formulations. Elevated temperature improved the characteristics of drug-loaded nanogels at intermediate solvent ratios. Compared to batch synthesis, the microfluidic process offers enhanced reproducibility and size control. Conclusions: Microfluidic SPAAC synthesis enables precise and scalable fabrication of PGA NGs with controllable size and drug loading. This platform supports future integration of on-chip purification and monitoring for clinical nanomedicine applications.

An electrochemical aptasensor based on Ti3C2Tx (MXene) and cDNA-PAA was established for sensitive detection of aflatoxin B1 (AFB1) in peanuts. The high specific surface area of Ti3C2Tx (MXene) contributed to improve electrochemical efficiency and enhancing sensor stability which were characterized by the Randles-Sevcik equation. The self-made polyacrylic acid (PAA) nanogel was added with aptamer complementary chain (cDNA) to form cDNA-PAA nano gel composite, which could realize the synergistic amplification of the difference between the electrochemical signals before and after the addition of AFB1. The sensing effect of cDNA-PAA was validated using DPV. Methylene blue (MB) was modified at the proximal 3' termini of the aptamer (Apt-MB), meanwhile AuNPs was used to immobilize Apt-MB and improve the efficiency of electrochemical reactions. The competition between AFB1 and cDNA-PAA combined with Apt MB resulted in a significant change in the electrochemical signal current. In addition, the constructed electrochemical aptasensor had a lower detection limit of 1.0 × 10-3ng/L for AFB1 under optimal detection conditions, and a detection range of 1 to 1000ng/L. Moreover, peanuts with different concentrations of AFB1 were used as actual detection samples. Through the constructed sensor detection, the spiked recovery rates within the spiking range of 50 to 500ng/mL were 97.76% to 101.84% (n = 3).

CRISPR/Cas9-mediated programmable gene editing has disrupted the biotechnology industry since it was first described in 2012. Safe in vivo delivery is a key bottleneck for its therapeutic use. Viral vector-mediated delivery raises concerns due to immunogenicity, long-term expression, and genomic disruption. Delivery of pre-complexed ribonucleoprotein (RNP) reduces off-target effects, and recombinant Cas9 production is more cost-effective than viral vector synthesis. CRISPR-Cas RNPs do not possess intrinsic cell entry mechanisms, and physical delivery methods are confined to ex vivo editing, necessitating non-viral delivery approaches. Nanogels (NG) are biocompatible polymeric nanoparticles capable of entrapping proteins. Here, we report the first proof of principle that NGs from thiol-functionalized polyglycidol can entrap active RNPs with high efficiency (60 ± 2%). We call these particles CRISPR-Gels. A commercially available E. coli lysate for cell-free transcription and translation (TXTL) was used to mimic the intracellular reductive degradation of NGs while providing a real-time fluorescence readout of RNP activity. Degradation and RNP activity were observed within 30–90 min. The described TXTL assay can be utilized to evaluate the release of RNP in a cytosol-mimicking environment from redox-sensitive nanoparticles in a high-throughput and cost-effective way. Further studies are needed to assess the in vitro and in vivo performance of CRISPR-Gels.Supplementary InformationThe online version contains supplementary material available at 10.1186/s11671-025-04316-5.

Mucoadhesive nanoparticles show promise for mucosal drug delivery, but ocular applications remain limited by rapid clearance, poor retention, and insufficient drug encapsulation. Existing systems struggle to deliver a full spectrum of therapeutics, hydrophobic drugs, hydrophilic drugs, and proteins, despite the critical need for such versatility in treating complex ocular diseases. Many eye conditions, including infection, inflammation, and degenerative disorder, require combination therapies or multidrug regimens for optimal therapeutic outcomes. To address these limitations, we developed a biocompatible tannic acid (TA)-cross-linked nanogel (NG) platform with robust mucoadhesion, anti-inflammatory, reactive oxygen species (ROS) scavenging properties, and sustained drug-release capabilities. The NGs were synthesized from a temperature-responsive poly(ethylene glycol)-based copolymer that self-aggregates above its lower critical solution temperature and is cross-linked with TA. TA's polyphenolic structure enables multimodal mucoadhesion and antioxidant activity, enhancing ocular retention and protecting against ROS-induced damage. The NGs achieved high loading efficiency (>80%) for diverse therapeutics, including moxifloxacin, a hydrophilic antibiotic; dexamethasone (Dex), a hydrophobic anti-inflammatory drug; as well as bovine serum albumin, used as a model protein to explore potential for protein encapsulation. In proof-of-concept studies, Dex-loaded NGs demonstrated sustained release (>24 days) and therapeutic efficacy in vitro and in vivo. Blank NGs also exhibited anti-inflammatory activity in vivo, comparable to Dex-loaded NGs in an acute model of ocular inflammation, demonstrating their intrinsic therapeutic potential. By enabling delivery of multiple therapeutic classes while providing inherent anti-inflammatory function, this TA-cross-linked NG platform offers a versatile and effective strategy for managing complex ocular diseases.

Abstract The multi-stimuli-responsive nanohydrogels provide a powerful strategy for enhancing drug utilization, preservation, controlled release, and minimizing systemic toxicity. Herein, we designed and developed a new multi-stimuli-responsive magnetic graphene oxide (MGO) integrated carboxymethyl cellulose/κ-carrageenan (CMC/CG/MGO) nanogels (NGs) for colon-specific delivery of sunitinib (SU). The physicochemical properties of the CMC/CG/MGO NGs were investigated by various analytical techniques of XRD, FTIR, TGA VSM, DLS, BET, and FESEM/TEM. The in-vitro SU release results exhibited that the CMC/CG/MGO NGs have a sustained release behavior with good pH, magnetic field, and near-infrared (NIR) light-dependent properties. The integrated photothermal agent MGO endowed the CMC/CG NGs with efficient photothermal properties, enabling precise SU release control under NIR laser irradiation. The CMC/CG/MGO/SU NGs displayed a good photothermal conversion effect (η = 38.5%). Besides, the CMC/CG/MGO NGs were not cytotoxic (cell viability &gt; 73% at 15.6–500 ppm) for the L929 fibroblast and Caco-2 cell lines. The MTT results also revealed that the CMC/CG/MGO/SU NGs exhibited enhanced anti-cancer activity compared to free SU under NIR laser irradiation. These results highlight the potential of CMC/CG/MGO/SU NGs as a promising candidate for remotely controlled multi-stimuli-responsive drug delivery. Graphical abstract

Background: Chitosan (CS) crosslinked with genipin (GNP) provides a mild, non-toxic route to generate nanogels (NGs) with enhanced integrity and colloidal stability. Objectives: To develop and characterise CS-GNP NG as a novel platform for targeted cellular delivery, optimising design through physicochemical characterisation and biocompatibility evaluation. Methods: NGs were synthesised under optimised conditions by adjusting the pH of the CS solution, followed by high-intensity ultrasound (HIUS) to achieve disaggregation. Physicochemical characterisation was carried out using UV-Vis spectroscopy, FTIR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). Rheological studies and SAXS analysis assessed structural properties. Biocompatibility was evaluated via MTT assay, and internalisation was monitored by fluorescence microscopy on mammalian cell lines. Results: NG formation was highly pH-dependent, with optimal configuration at pH 4.5, yielding stable, uniformly sized particles (~200 nm, ζ-potential +29 mV). Kinetic modelling showed a sigmoidal formation pattern, suggesting nucleation, growth, and stabilisation. FTIR confirmed covalent bonding between CS and GNP via primary amide bonds and Schiff bases. Rheology indicated pseudoplastic behaviour, and SAXS revealed a compact network formation. Biocompatibility assays confirmed non-cytotoxicity below 100 µg/mL and efficient cellular uptake. Conclusions: This study presents a rapid, reproducible protocol for generating colloidally stable, biocompatible NGs suitable for drug delivery.

Progress in the design of chitosan-based nanogels for folic acid delivery for ocular applications.

Phosphate functionalization of nanogels (NGs), originally designed to enhance interactions with fungal pathogens, also significantly influences their immune interactions and systemic behaviour. In this study, we investigated how phosphate-modified NGs perform as antifungal carriers in vivo using the silkworm model. We found that phosphate functionalization promotes faster internalization by granulocytes-immune cells functionally similar to mammalian neutrophils-highlighting a trade-off between antifungal activity and immune uptake. In parallel, phosphate-functionalized NGs exhibited prolonged circulation, more consistent biodistribution patterns, and reduced batch variability compared to unmodified NGs. These features contributed to superior and more reproducible in vivo antifungal efficacy when delivering itraconazole. Importantly, the biodistribution profiles observed in silkworms aligned well with previous mammalian data, further validating silkworms as an efficient, cost-effective model for early-stage evaluation of nanocarrier systems. Our findings underscore the importance of tuning surface functionalization to balance immune interaction and therapeutic performance, providing valuable insights for optimizing systemic antifungal nanotherapies.

Sepsis is featured by uncontrolled life-threatening systemic inflammatory responses to infection and tissue damage. Spontaneous attenuation of a broad spectrum of septic molecules and cytokines is promising for effective sepsis treatment. We have developed a functionalized nanosized hydrogel, i.e., nanogel (NG), via a one-pot precipitation polymerization using biocompatible, biodegradable monomers/cross-linkers and versatile polymerizable functional telodendrimer (TD) nanotraps (NTs) for effective scavenging of septic molecules. The telodendrimer nanogel (TD-NG) has a spherical morphology with a homogeneous size distribution around 300 nm. TD-NG is stable in plasma and can be degraded in the presence of reducing agents, e.g., intracellular glutathione. The size-exclusive nanogel network and the polyethylene glycol (PEG) shell coating exclude the abundant serum proteins for selective and effective capture of septic molecules, e.g., lipopolysaccharide (LPS), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. PEGylated TD-NGs are nontoxic in cell culture with low immune cell uptake and biocompatible after iv injection with prolonged circulation time and majority elimination into feces via liver bile ducts. Systemic administration of TD-NG significantly inhibits LPS-induced NF-κB activation and cytokine production. PEGylated TD-NGs effectively attenuate inflammatory molecules in situ for effective immune modulation, which ameliorates tissue damage and improves the survival rate in severe sepsis mouse models induced by cecum ligation and puncture.

Nanogels (NGs) are presently the focus of extensive research because of their special qualities, including minimal particle size, excellent encapsulating efficacy, and minimizing the breakdown of active compounds. As a result, NGs are great candidates for drug delivery systems. Cross-linked nanoparticles (NPs) called stimulus-responsive NGs are comprised of synthetic, natural, or a combination of natural and synthetic polymers. These NPs can swell in response to large amounts of solvent, but their structural makeup prevents them from dissolving. Furthermore, in response to (i) physical stimuli like temperatures, ion strength, and magnetized or electrical fields; (ii) chemical stimuli like the pH level, molecules, or ions; (iii) biological stimuli like the enzymatic substrate or affinity ligand, they transform into a hard particle (collapsed form) from a polymer solution (swell form). Over the past decade, there has been a major advancement in the creation of "smart" NGs in applications related to therapeutics and diagnosis, involving nucleic acid and intracellular drug delivery, photodynamic/photothermal treatment, biological imaging, and its detection. The nanogels reviewed in this article rely only on temperatures, pH, light, magnetic fields, and combinations of those variables. Developing a targeted delivery vehicle will greatly benefit from the presented information, especially when used for Core-shell multi-sensitive photo-sensitive nanogels.

The development of advanced drug delivery systems that offer precise, controlled, and sustained release of therapeutic agents remains a significant challenge, particularly for applications in oncology where effective targeting and prolonged drug exposure are essential. We synthesized and characterized a multistimuli-responsive magnetic nanogel-hydrogel nanocomposite (MNHNC) designed for controlled and extended drug release, with an emphasis on anticancer drug delivery. The MNHNC was developed by incorporating poly(N-isopropylacrylamide-co-acrylamide) (p(NIPAM-co-AAm)) nanogels (NGs) within a net-shaped salep-grafted poly(acrylic acid) (PAA) hydrogel matrix, coupled with in situ formation of Fe3O4 nanoparticles to introduce magnetic responsiveness and serve as a cross-linking agent. The nanocomposite exhibited notable swelling capabilities, achieving equilibrium values of 706 g/g at pH 9 (25 °C) and 603 g/g at physiological temperature (37 °C, pH 7.4). Additionally, MNHNC demonstrated responsiveness to pH, temperature, and magnetic fields, facilitating controlled drug release. Using doxorubicin (DOX) as a model drug, MNHNC exhibited dual pH sensitivity (NG at pH 5.4 and MNHNC at pH 7.4) and achieved a prolonged release profile of 400 h, significantly surpassing conventional systems, including our previous nanocomposite. Release kinetics followed a super case-II transport mechanism, where swelling primarily governed drug diffusion. Furthermore, the application of a magnetic field enabled fine-tuning of the release rate, offering an additional layer of control. The kinetic study indicated that the drug release from MNHNC followed zero-order kinetics under certain conditions, ensuring a consistent release rate over time, which is highly desirable for maintaining therapeutic efficacy. The Korsmeyer-Peppas model further confirmed the super case-II transport mechanism, highlighting the significant influence of polymer relaxation and swelling on the release process. The Hixson-Crowell model also demonstrated the role of matrix erosion in the drug release mechanism. The results showed a marked improvement in pH and temperature sensitivity compared to previous formulations, enhanced mechanical stability due to the integration of Fe3O4 nanoparticles, and the ability to modulate drug release through external magnetic fields. In vitro cytotoxicity assessment using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay demonstrated the biocompatibility of the MNHNC, with over 95% cell viability in the absence of DOX, confirming its nontoxic nature. Upon DOX loading, MNHNC exhibited a proper anticancer effect against cancer cell lines, showing a dose-dependent reduction in cell viability. The robust mechanical stability, biocompatibility, and multistimuli responsiveness of MNHNC position it as a promising candidate for advanced, targeted drug delivery systems.

Objective: This study evaluates the antimicrobial activity of pomegranate (Punica granatum L.) peel extract in vitro and the anti-inflammatory effects of its nano gel formulation in vivo on gingival inflammation in male wistar rats. Methods: The antimicrobial activity was tested against Aggregatibacteractinomycetemcomitans, Porphyromonasgingivalis, and Fusobacterium nucleatum using ethanol, ethyl acetate, and n-hexane extracts at concentrations of 0.8–25%. The anti-inflammatory effect was assessed using pomegranate peel extract nano gel (6.25%, 12.5%, and 25%) in a ligature-induced gingivitis model in Wistar rats, with Gengigel as a positive control. Evaluation parameters included inhibition zone diameters for antimicrobial activity, while histological analysis of lymphocyte, neutrophil, and macrophage counts was conducted on days 3 and 7 to assess anti-inflammatory effects. Results: The 25% ethanol extract exhibited the highest antimicrobial inhibition zones (16.95 mm for A. actinomycetemcomitans, 16.83 mm for P. gingivalis, and 16.35 mm for F. nucleatum, p&lt;0.05). The 25% nano gel formulation significantly reduced inflammatory cell counts compared to the control (p&lt;0.05), showing reductions in lymphocytes (4.33±1.53), neutrophils (1.00±0.00), and macrophages (1.67±0.57) by day 7. Conclusion: Pomegranate peel extract demonstrated potent antimicrobial properties, especially in ethanol-based formulations. The nano gel formulation exhibited significant anti-inflammatory effects, with the 25% concentration proving the most effective in reducing gingival inflammation. These findings highlight its potential as a natural therapeutic agent for periodontal disease management.

Biocompatible nanogels with tunable size and tailorable properties: A simple synthesis by self-assembly and disulfide crosslinking of amphiphilic hyperbranched peach gum polysaccharide.

Compacting hyaluronan into nanogels induces an enhanced macropinocytosis in MC38 cells.

Lung cancer is the second most common Cancer in the United States; however, it remains the leading cause of cancer-related death in the United States and worldwide. 5-fluorouracil (5-FU) is among the most administrated chemotherapeutic agents for various neoplasms. This study focused on synthesizing and characterizing P(AAm/SA)/5-Fu nanogels as a potential drug delivery system. The nanogels were prepared by combining sodium alginate (SA) and acrylamide (AAm) monomers, followed by gamma irradiation-induced polymerization at a dose of 5kGy. Then, the obtained nanogel was loaded with 500ppm of 5-Fu. Transmission electron microscopy (TEM) imaging was utilized to characterize the nanogels' morphology and monodispersity with a particle size of (50nm). Rats were randomly assigned to four groups (six animals per group): Group 1: (Control): normal healthy. Group 2: Cancer-bearing animals (animals injected with diethylnitrosamine (DEN) 20mg/kg body weight for 3months. Group 3: Cancer+ 5-fluorouracil (12mg/kg body weight). Group4: Cancer+ 5-Flurouracil- Loaded P (AAm/SA) Nanogel. DEN markedly increased PTGS2, Cox2, PKB, PFKm, and ERK1 levels. Also, observed up-regulation in ALKBH5, Beclin1, ULK1, and P53 gene expressions in the cancer-bearing animal group compared with the control group. 5-fluorouracil nano gel significantly ameliorated the above-mentioned parameters and immunohistochemistry study. 5-fluorouracil nanogel significantly ameliorated the parameters mentioned above, as well as the immunohistochemistry study. The 5-FU-loaded P(AAm/SA) nanogel could serve as a promising approach for targeting tumor cell proliferation, speeding up autophagic processes, and overcoming chemotherapy resistance in lung carcinoma.