Search Results (293)

Background/Objectives: This paper describes the synthesis of silica nanoparticles (SiNPs) and their surface modification with amino and phosphate groups (SiNPs-NH₂-PO₃). The functionalized nanoparticles were subsequently loaded with the anticancer drug 5-fluorouracil (SiNPs-NH₂-PO₃-5-FLU) and further modified with PEG2000 (SiNPs-NH₂-PO₃-5-FLU-PEG2000). Methods: In this study, a one-step, two-phase, sol–gel method carried out at room temperature was used to synthesize the nanoparticles. The size and surface zeta potential of the created SiNPs were determined by DLS measurements. HPLC was used to determine the amount of drug loaded into silica nanoparticles and the drug release profile in two different pH environments (slightly acidic and physiological). Based on physicochemical characteristics, the SiNPs-NH₂-PO₃-5-FLU and SiNPs-NH₂-PO₃-5-FLU-PEG2000 formulations were chosen for comprehensive characterization. The cytotoxicity of the studied complexes was assessed in MCF7 breast cancer cells, while their ability to induce apoptosis in those cells was examined using specific immunofluorescence markers: active caspase-7, active poly(ADP-ribose) polymerase (PARP), and p53 protein. Results: Our findings demonstrate that SiNPs-NH₂-PO₃-5-FLU can induce a stronger apoptotic response than free 5-FLU at equivalent concentrations. We observed that drug release occurs not only under physiological conditions but is further enhanced in a mildly acidic environment (pH 5.0), characteristic of the tumor microenvironment. Conclusions: Most 5-fluorouracil formulations are administered as injectable solutions, resulting in systemic exposure and significant adverse effects. However, their encapsulation within nanoparticles could favor preferential drug release in the acidic tumor microenvironment, thus supporting targeted therapy and reducing toxicity to healthy tissues. Moreover, PEGylation of the nanoformulation allows prolonged and controlled release. Full article

Dispersion stabilization of nanoparticles for catalytic reactions is an important issue. However, dispersing agents should be carefully selected not to hinder catalytic performance. In the present study, physisorption of cyclic poly(ethylene glycol) (c-PEG) onto platinum nanoparticles (PtNPs) was investigated in comparison with unmodified PtNPs (PtNPs/No PEG), PtNPs mixed with linear PEG (PtNPs/HO-PEG-OH), and PtNPs chemisorbed with HS-PEG-OMe (PtNPs/HS-PEG-OMe). DLS showed a significant increase in the particle size for PtNPs/c-PEG and PtNPs/HS-PEG-OMe compared to PtNPs/No PEG and PtNPs/HO-PEG-OH. ζ-potential measurements revealed values around −30 mV for PtNPs/No PEG and PtNPs/HO-PEG-OH, whereas PtNPs/c-PEG and PtNPs/HS-PEG-OMe approached 0 mV, which indicated that c-PEG and HS-PEG-OMe adsorb onto PtNPs to form a shielding layer. Moreover, PtNPs/c-PEG and PtNPs/HS-PEG-OMe were stable in a phosphate-buffered saline (PBS) solution, but PtNPs/No PEG and PtNPs/HO-PEG-OH immediately aggregated. This suggests that high dispersion stability by c-PEG is comparable to ordinary surface modification using HS-PEG-OMe. Furthermore, the catalytic ability of PtNPs/c-PEG and PtNPs/HS-PEG-OMe was compared in various reactions. As a result, physisorbed PtNPs/c-PEG showed suitable catalytic activities, whereas chemisorbed PtNPs/HS-PEG-OMe was significantly hampered by the blocking of the catalytic sites with thiol in some reactions. Thus, physisorption of c-PEG endows PtNPs with dispersion stability and maintains the catalytic ability, leading to an alternative way of modifying metal nanoparticles. Full article

In this current study, beech wood (Fagus sylvatica) was modified by cross-linking via esterification with combinations of polyethylene glycol (PEG) 400 and various carboxylic acids. Promising combinations (1,2,3,4-butanetetracarboxylic acid (BTCA)/PEG400; citric acid (CA)/PEG400; malic acid (MA)/PEG400) were examined in previous studies. The goal of this study was the optimisation of the treatment. The use of a catalyst, the concentration of the chemicals and the curing conditions were varied. The weight percentage gain (WPG), bulking and anti-swelling efficiency (ASE) after leaching in water were used to evaluate the success of modification. Optimal results were achieved with a curing temperature of 160 °C. Without the addition of PEG, the WPG and bulking values were lower. The use of sodium hypophosphite monohydrate (SHP) as a catalyst had a positive effect only on the combination of BTCA/PEG400. Variations of concentrations usually had a higher impact on WPG and bulking than on ASE. The combination of MA/PEG 400 generally showed lower values. Full article

Background/Objectives: Bone-targeted drug delivery systems hold great promise for treating skeletal diseases, yet the optimal strategy for functionalizing lipid nanoparticles (LNPs) with bone-homing ligands remains insufficiently explored. Herein, we compared two alendronate sodium (Alen) modification approaches (pre-conjugation and post-conjugation) for constructing bone-targeted LNPs capable of delivering mRNA to skeletal tissues. Methods: LNPs were fabricated via microfluidic mixing, and the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-alendronate conjugate (DSPE-PEG-Alen) required for the pre-conjugation method was synthesized. The bone-targeting ability of LNPs prepared by the two Alen modification strategies was evaluated using an in vitro hydroxyapatite (HAP) binding assay. Furthermore, the physicochemical properties, bone-targeting performance, mRNA delivery efficiency, and biosafety of the LNPs prepared by the post-conjugation method were assessed through cellular uptake, in vivo imaging, and other methods. Results: Hydroxyapatite binding assays revealed that the post-conjugation strategy afforded significantly superior bone affinity compared to the pre-conjugation approach. In addition, ex vivo bone fragment binding experiments further confirmed that the bone-targeting LNPs prepared by the post-conjugation method exhibited stronger bone-binding capability compared to unmodified LNPs. The optimized Alen-LNPs demonstrated efficient cellular uptake and functional mRNA translation in bone marrow mesenchymal stem cells with negligible cytotoxicity. In vivo studies in mice confirmed the preferential accumulation of Alen-LNPs in bone tissues, with successful green fluorescent protein (GFP) mRNA translation detected in bone tissue sections. Histopathological analysis confirmed the biosafety of the formulation. Conclusions: This study establishes the post-conjugation strategy as the superior approach for Alen functionalization of LNPs, providing a robust and reproducible platform for bone-targeted mRNA therapeutics. Full article

Upconverting nanoparticles, which transform low-energy infrared radiation into high-energy visible or UV light, show great potential in today’s technology. High-quality upconversion colloid (UCC) consisting of lanthanide-based nanoparticles with a diameter of ~10 nm was obtained using a combination of two processes: high-temperature coprecipitation and hydrothermal treatment in an autoclave. The UCC was then PEGylated with PEG-alendronate (PEG-Ale) to facilitate its dispersion in aqueous cell culture media intended for in vitro cell uptake assays. The surface modification of the nanoparticles increased both the colloidal stability in water and the upconversion emission by mitigating surface quenching. UCC@Ale-PEG was characterized by transmission and scanning electron microscopy, dynamic light scattering, and fluorescence microscopy detecting upconversion photoluminescence emission. The results of an in vitro assay revealed that this new generation of UCC can be internalized by various cell types, including epithelial cells and macrophages, upon several hours of exposure, suggesting broad application potential of this type of UCC in biomedicine, bioengineering, and environmental sciences. Full article

Drought is a major environmental threat to agriculture. This study examined the role of anthocyanins in plant drought tolerance by comparing two basil varieties differing in leaf anthocyanin content: green basil (Ocimum basilicum L. Italiano Classico) and purple basil (Ocimum basilicum L. Dark Opal). The impact of the PEG-induced drought stress was assessed by monitoring changes in chlorophyll a fluorescence parameters (JIP and PAM), leaf pigment content, anthocyanin and total phenolic levels, oxidative stress markers (malondialdehyde, hydrogen peroxide and membrane integrity), as well as radical-scavenging capacity (DPPH assay). Drought stress led to a modification on both the donor (Wk) and acceptor (Vj) sides of PSII, which influences Q_A reoxidation and amounts of the closed reaction centers (1-qP). These changes inhibited photosystem II photochemistry, the rate of the electron transport (ETR), and the rate of the photosynthesis (R_Fd) and decreased performance indices (PI_ABS, PItotal), as well as the photosystem I photochemistry. The drought-induced changes were associated with an increase in the dissipated energy per reaction center (DI₀/RC). The results show that photosynthetic functions in purple basil were less affected under drought stress compared to green basil. The reason for better tolerance of purple basil is associated with elevated anthocyanin levels, which correlate with enhanced antioxidant capacity, reduced hydrogen peroxide accumulation, lower membrane lipid peroxidation, improved relative water content and membrane stability. In addition, rapid cyclic electron flow around photosystem I and a higher carotenoid to chlorophyll ratio contribute to drought tolerance in purple basil. After re-watering, purple basil recovers its photosynthetic function almost completely, unlike green basil, which shows further suppression. The increase in the anthocyanin content and radical-scavenging capacity, as well as the smaller oxidative damage under drought stress, are the main reasons for the better recovery in purple basil. Overall, the findings highlight that higher anthocyanin accumulation in purple basil confers greater drought tolerance and recovery capacity by stabilizing photosynthetic processes and reducing oxidative stress. Full article

The development of effective inhalable drugs remains a key challenge in the treatment of pulmonary diseases, due to the physiological barriers of the respiratory tract and the lack of predictive models that accurately reproduce the human lung environment. In this context, liposomes (LP) have emerged as promising nanocarriers for pulmonary drug delivery due to their high biocompatibility, surfactant-like composition, capacity to encapsulate both hydrophilic and lipophilic drugs, and potential to provide sustained drug release while reducing systemic toxicity. This study evaluates the influence of size and PEGylation on their physicochemical properties, cytotoxicity, interaction with the pulmonary mucus, and cellular internalisation. LP of 100 nm (LP 100), 200 nm (LP 200), and 600 nm (LP 600) were characterised physiochemically and evaluated in pulmonary cell lines (A549 and Calu-3) exposed in liquid–liquid interface (LLI) and air–liquid interface (ALI) by nebulisation. In addition, artificial pulmonary mucus (APM) was employed to analyse LP penetration through the pulmonary mucus barrier. Results indicate that LP 100 exhibits greater colloidal stability, lower cytotoxicity, and sustained migration through the APM over time with respect to larger particles. PEGylation of LP 100 (LP-PEG) further increases their stability and ability to penetrate the APM, although cellular internalisation is reduced due to the steric effect of the PEG coating. These findings highlight the importance of adjusting the size and surface modifications of LPs according to the therapeutic target of the drug, optimising their persistence on the epithelial surface or their cellular uptake. Full article

Background: Chronic diabetic wounds, particularly diabetic foot ulcers (DFUs), are prone to recurrent infection and delayed healing, resulting in substantial morbidity, mortality, and economic burden. Multifunctional wound dressings that combine antibacterial, antioxidant, conductive, and self-healing properties may help to address the complex microenvironment of chronic diabetic wounds. Methods: In this study, ε-poly-L-lysine and amino-terminated polyethylene glycol were grafted onto carboxylated single-walled carbon nanotubes (SWCNTs) via amide coupling to obtain ε-PL-CNT-PEG. Aminated chondroitin sulfate (CS-ADH) and a catechol–metal coordination complex of protocatechualdehyde and Fe³⁺ (PA@Fe) were then used to construct a dynamic covalently cross-linked hydrogel network through Schiff-base chemistry. The obtained hydrogels (Gel0–3, Gel4) were characterized for photothermal performance, rheological behavior, microstructure, swelling/degradation, adhesiveness, antioxidant capacity, electrical conductivity, cytocompatibility, hemocompatibility, and antibacterial activity in the presence and absence of near-infrared (NIR, 808 nm) irradiation. Results: ε-PL-CNT-PEG showed good aqueous dispersibility, NIR-induced photothermal conversion, and improved cytocompatibility after surface modification. Incorporation of ε-PL-CNT-PEG into the PA@Fe/CS-ADH network yielded conductive hydrogels with porous microstructures and storage modulus (G′) higher than loss modulus (G′′) over the tested frequency range, indicating stable gel-like behavior. The hydrogels exhibited self-healing under alternating strain and macroscopic rejoining after cutting. Swelling and degradation studies demonstrated pH-dependent degradation, with faster degradation in mildly acidic conditions (pH 5.0), mimicking infected chronic diabetic wounds. The hydrogels adhered to diverse substrates and tolerated joint movements. Gel4 showed notable DPPH• and H₂O₂ scavenging (≈65% and ≈60%, respectively, within several hours). The electrical conductivity was 0.19 ± 0.0X mS/cm for Gel0–3 and 0.21 ± 0.0Y mS/cm for Gel4 (mean ± SD, n = 3), falling within the range reported for human skin. In vitro, NIH3T3 cells maintained >90% viability in the presence of hydrogel extracts, and hemolysis ratios remained below 5%. Hydrogels containing ε-PL-CNT-PEG displayed enhanced antibacterial effects against Escherichia coli and Staphylococcus aureus, and NIR irradiation further reduced bacterial survival, with some formulations achieving near-complete inhibition under low-power (0.2–0.3 W/cm²) 808 nm irradiation. Conclusions: A dynamic, conductive hydrogel based on PA@Fe, CS-ADH, and ε-PL-CNT-PEG was successfully developed. The hydrogel combines photothermal antibacterial activity, antioxidant capacity, electrical conductivity, self-healing behavior, adhesiveness, cytocompatibility, and hemocompatibility. These properties suggest potential for application as a wound dressing for chronic diabetic wounds, including diabetic foot ulcers, although further in vivo studies are required to validate therapeutic efficacy. Full article

This paper presents the optimization of surface modification for aptameric graphene nanosensors for the measurement of biomarkers in undiluted physiological media. In these sensors, graphene transduces the binding between an aptamer and the intended target biomarker into a measurable signal while being coated with a polyethylene glycol (PEG) nanolayer to minimize nonspecific adsorption of matrix molecules. We perform a systematic study of the aptamer and PEG attachment schemes and parameters, including the impact of the serial or parallel PEG–aptamer attachment scheme, PEG molecular weight and surface density, and aptamer surface density on the sensor behavior, such as the responsivity to biomarker concentration changes, and importantly, they are used for operation in physiological media and have the ability to reject nonspecific binding to interfering molecules. We then use the understanding from this parametric study to identify graphene nanosensor designs that are optimally functionalized with PEG and aptamers to be strongly responsive to target biomarkers and effectively reduce nonspecific adsorption of interferents, thereby enabling sensitive and specific biomarker measurements in undiluted physiological media. The experimental results show that nanosensors that were optimized via serial modification with 5000 Da PEG at 15 mM and a 94 nt DNA aptamer at 500 nM allowed specific measurement of C-reactive protein (CRP) in undiluted human serum with a limit of detection (LOD) down to 27 pM, representing an up to 1000-fold improvement compared to previously reported CRP measurements. Full article

Controlling cell attachment to substrates with spatiotemporal precision is a key technological foundation in fields such as tissue engineering, cell sorting, and cell–cell interaction analysis. Among existing approaches, azobenzene-based photocontrollable systems offer a promising strategy for the reversible regulation of cell adhesion. However, most conventional systems rely on the intrinsic adhesion capacity of adherent cells. Consequently, although the importance of non-adherent cell types has grown in biomedical research, their dynamic manipulation remains insufficiently explored. In this study, we developed a versatile system to control cell adhesion based on host–guest interactions between an azobenzene–lipid conjugate and a cyclodextrin-functionalized substrate. Using human chronic myelogenous leukemia (K562) cells, we successfully demonstrated photocontrolled adhesion and detachment, confirming the applicability of this system to non-adherent cells. Furthermore, we quantitatively measured the adhesion force and observed an inverse correlation between adhesion efficiency and adhesion force for different PEG linker lengths (2k, 4k, and 8k). This finding demonstrates the critical role of the linker length in effective cell surface modification. In conclusion, the proposed system establishes a photocontrollable adhesion method applicable to non-adherent cells, demonstrating its potential as a versatile technology for broad applications. Full article

Lipid nanoparticles (LNPs) are now the go-to method for delivering genetic medicines, backed by real-world use in patients. Things like which fats they are made of, their shape at the molecular level, how ingredients mix, and how they are built, matter a lot. This review attempts to take a close look at how different components, such as ionizable lipids, auxiliary lipids (DSPC, DOPE), cholesterol, and PEG-based lipids, affect the bioavailability of LNPs. It also focuses on key functions of LNPs, including packaging genetic material, escaping cellular traps, spreading in the body, and remaining active in the blood. New data show that lipids with the right handedness and highly sensitive chiroptical quality control can sharpen delivery accuracy and boost transport rates, turning stereochemistry into a practical design knob. Rather than simply listing results, we examine real-world examples that are already used to regulate gene expression, enhance mRNA expression, splenic targeting, and show great potential for gene repair, protein replacement, and DNA base-editing applications. Also, recent advances in AI-based designs for LNPs that take molecular shape into account and help speed up modifications to lipid arrangements and mixture configurations are highlighted. In summary, this paper presents a practical and scientific blueprint to support smarter production of advanced LNPs used in genetic medicine, addressing existing obstacles, balanced with future opportunities. Full article

In this study, surface-modified bio-based hydrogels derived from crosslinked quaternized chitosan (MQCGs) were developed to treat PFAS-contaminated water. The novelty of this work lies in the surface modification and engineering of the hydrogels to enhance the surface area and positive charge of the hydrogels through sacrificial templating. By blending the chitosan solution with polyethylene glycol (PEG) and then removing PEG via sacrificial templating, microscale channels were created on the surface of the hydrogels. This increased the availability of the hydrogel’s positive charges for increased electrostatic interactions with PFAS, achieving >98% PFOS (a long-chain PFAS) adsorption in less than 30 min. Batch adsorption experiments demonstrated that surface-modified quaternized chitosan hydrogels (MQCGs) removed both long- and short-chain PFAS across a pH range of 3 to 12, maintaining their performance over 10 regeneration cycles. The adsorption behavior followed the Freundlich isotherm model and pseudo-second-order kinetics, indicating fast multilayer adsorption on heterogeneous active sites via the combined actions of electrostatic, hydrophobic, and physical interactions. Using PFOS and PFOA as model long-chain PFAS and PFBS and PFHxA as short-chain surrogates, respectively, MQCGs achieved a complete removal of PFOS and PFOA and over a 99.9% removal of PFBS and PFHxA, each at a low concentration of 500 µg/L in water. Moreover, MQCGs exhibited highly efficient removal of PFAS at environmentally relevant concentrations of 20 µg/L in tap water containing MgSO₄ and NaCl as competing electrolytes, demonstrating the potential of MQCGs as a new class of efficient, selective, and regenerable materials for PFAS sequestration. Full article

Polydimethylsiloxane (PDMS) is widely used in microfluidics and medical devices; however, its inherent hydrophobicity limits its applications. This can be resolved by the formation of polyethylene glycol (PEG)-based hydrophilic coatings. Here, we aimed to prove that PDMS surfaces modified with low molecular weight PEG (400) provided a more stable hydrophilic surface. The lowest contact angle achieved via using PEG400 and the “grafting from” approach was 8.6 ± 3.5°. Under perfusion conditions, imitating arterial and capillary flows, such coatings were considerably stable, and the contact angle was kept at 45.5° after 3 days. Moreover, the applied surface modifications preserved surface roughness, elastic modulus, and optical transparency. Thus, these findings confirmed that the “grafting from” approach with low molecular weight PEG could be the most effective strategy to form hydrophilic PDMS coatings with optimal performance in biomedical applications. Full article

Microfluidic oxygenators promise to advance extracorporeal membrane oxygenation (ECMO) devices with enhanced hemodynamics and low prime volume. We are developing a silicon-based membrane oxygenator that will offer improved gas transfer and fluid flow control. Polyethylene glycol (PEG) has been used to improve hemocompatibility by providing excellent resistance to protein adsorption. Here, we characterized a polyethylene glycol surface modification of composite silicon–PDMS membranes to evaluate their effects on microfluidic oxygenator properties. X-ray photoelectron spectroscopy (XPS) and water contact angle goniometry confirmed successful PEG attachment, evidenced by the presence of characteristic C-O bonds and increased hydrophilicity, which was stable for 2 weeks. Oxygen flux tests demonstrated gas transfer rates as high as 89.6 ± 17.9 mL/min/m² and 50.8 ± 11.7 mL/min/m² for unmodified and PEG-coated membranes, respectively. Protein adsorption studies with human serum albumin (HSA) demonstrated a significant reduction in nonspecific protein binding on PEG-coated membranes with values as low as 14 ± 6 μg/cm². These studies expand on the characterization of our engineered oxygenator membranes and provide insight for the development of future surface optimization strategies to enhance hemocompatibility. Full article

Immune checkpoint inhibitors (ICIs) targeting PD-L1 and CD47 are clinically limited by severe off-target toxicities. To address this issue, immunotherapeutic prodrug strategies have been developed, aimed at preventing antibodies from binding to targets in healthy tissues and thereby reducing systemic toxicity. Existing strategies include prodrug technologies that mask the active sites of antibodies via peptide or polyethylene glycol (PEG) modification—yet these approaches also cause antibodies to lose their targeting ability. Herein, we propose an antibody prodrug strategy (termed FA-PEG-S-Ab) with active targeting capability. By modifying antibodies with folate-PEG-disulfide and PEG-disulfide linkages, we developed two novel prodrugs: FA-PEG-S-Atz (PD-L1-blocking prodrug) and FA-PEG-S-Hu5 (CD47-blocking prodrug). This strategy functions through two key steps: first, folate binding to folate receptor α (FRα)-mediated tumor-specific targeting enables the prodrugs to accumulate specifically in tumor tissues; subsequently, the high concentration of glutathione (GSH) in the tumor microenvironment (TME) specifically cleaves the disulfide bonds, removing the PEG shield, releasing the antibody, and restoring the antibody’s antigen-binding activity. In vitro experiments confirmed that the modified antibody prodrug FA-PEG-S-Hu5 exhibits high affinity for FRα (K_D = 4.02 × 10⁻⁹ M) and effectively masks the antibody’s binding activity (K_D from 1.05 × 10⁻¹¹ M to 2.10 × 10⁻⁸ M). Following activation by GSH in the TME, this masking effect is reversed, and the antibody regains its binding affinity (K_D = 2.14 × 10⁻¹⁰ M). Crucially, FA-PEG-S-Hu5 completely eliminates hemolytic toxicity. This “folate targeting delivery + TME activation” prodrug strategy is expected to provide a new solution for addressing the off-target toxicities of conventional ICIs. Full article