Polyethylene Glycol Modification Research Articles

Endogenous Protein-Modified Gold Nanorods as Immune-Inert Biomodulators for Tumor-Specific Imaging and Therapy.

Engineered modifications of nanomaterials inspired by nature hold great promise for disease-specific imaging and therapies. However, conventional polyethylene glycol modification is limited by immune system rejection. The manipulation of gold nanorods (Au NRs) modified by endogenous proteins (eP@Au) is reported as an engineered biomodulator for enhanced breast tumor therapy. The results show that eP@Au NRs neither activate inflammatory factors in vitro nor elicit rejection of immune responses in vivo. Tumor-specific eP@Au NRs exhibit a dual-modal imaging capability and trigger a mild photothermal effect under near-infrared light irradiation, enabling highly efficient imaging and therapy of tumors. Transcriptome sequencing and confirmatory experiments reveal that the antitumor effect is mainly attributed to the repression of PI3K-Akt/MAPK signaling pathways at the molecular level. This powerful and surprising in situ eP-regulated biomodulation demonstrates the advantages of convenient fabrication, inert immunogenicity, and biocompatibility, providing an alternative strategy for biomedical imaging and therapy.

Decorating channel walls in ordered macroporous ZIF-8 with hydrophilic PEG to immobilize lipase for efficient chiral resolution.

The development of efficient immobilization support for the enhancement of enzyme activity and recyclability is a highly desirable objective. Single-crystalline ordered macro-microporous ZIF-8 (SOM-ZIF-8), has emerged as a highly effective matrix for enzyme immobilization, however, the inherent hydrophobic nature limits its further advancement. Herein, we have customized the immobilization of the Pseudomonas cepacia lipase (LP) in the modification-channels of SOM-ZIF-8 by functionalizing the inner surface-properties with polyethylene glycol (PEG) (LP@SOM-ZIF-8-PEG), and significant enhancement of the activity and (thermal, solvent and cyclic) stability can be realized. The incorporation of PEG into SOM-ZIF-8 regulates its inner surface charge and hydrophobic properties, thereby enhancing enzyme loading, facilitating enzyme conformational adjustments, and achieving a uniform dispersion of LP in SOM-ZIF-8-PEG. LP@SOM-ZIF-8-PEG not only demonstrates a pronounced elevation in enzyme loading and activity over LP@SOM-ZIF-8 but also shows an enzyme activity that is impressively three times greater than LP@ZIF-8. It can completely resolve the 1-phenylethanol racemate in 60 min, with a conversion close to 50 % and an enantioselectivity of 99.8 %. After nine cycles of reuse, the LP@SOM-ZIF-8-PEG still holds onto 95 % of its initial activity. The excellent catalytic performance and stability of LP@SOM-ZIF-8-PEG, along with the universality of the PEG modification strategy for other enzymes, make this work promising in industrial applications.

Design and development of vaginal wall mimicking poly(ϵ-caprolactone) based nanofibrous prosthetic mesh for pelvic organ prolapse: evaluation of biocompatibility and antibacterial ability.

Mechanical non-conformance of conventionally used transvaginal non-degradable meshes has led to complications such as organ perforation, dyspareunia caused by mesh stiffness and stress shielding. In this study, we have solved the dire need to mimic the mechanical properties of the vaginal wall by designing and developing a soft and elastic mesh made of polycaprolactone (PCL), citric acid modified polyethylene glycol (PEGC) and zinc oxide (ZnO) prepared through electrospinning and testedin vitroandin vivo. The mesh containing 90:10:0.1 of PCL, PEGC and ZnO (PEGC-15 0.1ZnO mesh) conforms to the mechanical properties of the vaginal wall of the pelvic floor, has a burst strength of ∼35 N even after gamma-sterilization and 28 d of degradation inin vitro.In vitrostudies using adipose-derived stem cells revealed that the PCL-PEGC-15 0.1ZnO meshes were biocompatible and supported higher collagen production than commercial mesh.An in vitrobacterial adhesion study showed a 2-log reduction compared to commercially available mesh for prolapse treatment. Initial biocompatibility assessment in a rabbit model also showed that the PCL-PEGC-15 0.1ZnO mesh is biocompatible and supports fibrosis throughout the mesh. The softness and flexibility of the PCL-PEGC-15 0.1ZnO mesh based onin vitrotrials and initialin vivotrials show that the mesh has a potential clinical impact for pelvic floor repair treatment.

Asymmetrically PEGylated and amphipathic heptamethine indocyanine dyes potentiate radiotherapy of renal cell carcinoma via mitochondrial targeting

Enhancing the sensitivity of radiotherapy (RT) towards renal cell carcinoma (RCC) remains a challenge because RCC is a radioresistant tumor. In this work, we design and report asymmetrically Polyethylene Glycol (PEG)ylated and amphipathic heptamethine indocyanine dyes for efficient radiosensitization of RCC treatment. They were synthesized by modifying different lengths of PEG chains as hydrophilic moieties on one N-alkyl chain of a mitochondria-targeting heptamethine indocyanine dye (IR-808), and a radiosensitizer 2-nitroimidazole (NM) as a hydrophobic moiety on another N-alkyl chain. The PEG modification significantly improved water solubility, decreased the intermolecular π–π large aggregates, thereby enhanced renal excretion. The asymmetrical and amphipathic modification enhanced the preferential accumulation in renal tumors through self-assembly into small-size nanoparticles in aqueous environment. Radiosensitization was further improved by preferential accumulation in renal tumor cells and their mitochondria as mitochondria play a crucial role in rapid cancer cell growth, metastasis, and RT resistance. Additionally, the modification also increased the abilities of fluorescence emission and photostability, which is meaningful for imaging-guided precise RCC RT. Therefore, our findings may present a theranostic radiosensitizer for renal tumor-targeted imaging and radiosensitization.Graphical

Metal Doping Enabling Defective CoMo-Layered Double Hydroxide Nanosheets as Highly Efficient Photosensitizers for NIR-II Photodynamic Cancer Therapy.

Photodynamic therapy (PDT) is attracting widespread attention as a promising strategy for tumor treatment. However, the efficacy of PDT is severely limited by the insufficient tissue penetration depth of the light source and low reactive oxygen species (ROS) generation efficiency. Herein, the metal doping strategy is reported to construct a series of defect-rich M-doped amorphous CoMo-layered double hydroxide (a-M-CoMo-LDH, M = Mn, Cu, Al, Ni, Mg, Zn) photosensitizers (PSs) for NIR-II PDT. Especially, M-doped CoMo-LDH nanosheets are synthesized through a simple hydrothermal method and then etched by acid treatment to prepare defect-rich a-M-CoMo-LDH nanosheets. Under NIR-II 1270 nm laser irradiation, the defect-rich a-Zn-CoMo-LDH nanosheets exhibit the optimal PDT performance compared with other a-M-CoMo-LDH nanosheets, and also possess much higher ROS production activity (3.9 times) than that of the pristine a-CoMo-LDH, with a singlet oxygen quantum yield up to 1.86, which is the highest among all the reported PSs. After polyethylene glycol (PEG) modification, the a-Zn-CoMo-LDH-PEG nanosheets can function as an effective inorganic PS for PDT, effectively inducing cell apoptosis in vitro and eradicating tumors in vivo. Notably, transcriptome sequencing analysis and further molecular validation highlight the critical role of the apoptotic/p53/AMPK/oxidative phosphorylation signaling pathways in a-Zn-CoMo-LDH-PEG-induced cancer cell apoptosis.

Extraction, purification, structural characterization, bioactivities, modifications and structure-activity relationship of polysaccharides from Ophiopogon japonicus: a review.

Ophiopogon japonicus (Thunb.) Ker Gawl., is a traditional Chinese medicine (TCM) with a history of thousands of years. O. japonicus polysaccharides (OJPs), as one of the main active ingredient, are a kind of representative pharmacological bioactive macromolecules and mainly composed of Glc and Fru with molecular weight between 2.48 and 325 kDa. OJPs have a variety of biological activities, such as hypoglycemic, cardioprotective, immunomodulatory, improvement of obesity, and renal protective activity. In this review, the extraction, purification and structural characterization of OJPs were systematically reviewed, and its biological function, molecular mechanism and structure-activity relationship were analyzed. Additionally, this review summarized and found that structural modifications such as liposome modification, sulfation modification, and polyethylene glycol modification have improved the pharmacological activity and bioavailability of OJPs. Overall, this work will help to better understand OJPs and provide a theoretical review of their further development and utilization in the field of medicine and health food.

Electro-responsive hyaluronic acid-based click-hydrogels for wound healing

With the aim of healing challenging skin wounds, electro-responsive click-hydrogels made of hyaluronic acid (clickHA) crosslinked with a modified polyethylene glycol precursor (PEG) were prepared by semi-interpenetrating a conducting polymer, poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-MeOH) by oxidative polymerization. The porosity and pore size of the mixed hydrogel, clickHA/PEDOT-MeOH, were both higher than those determined for the hydrogel without PEDOT-MeOH, while a honeycomb-like morphology with PEDOT-MeOH covering the pore walls was observed. Although such PEDOT-MeOH-induced changes did not influence the water absorption capacity of clickHA, they drastically affected the mechanical and electrochemical behavior. More specifically, the semi-interpenetration of PEDOT-MeOH into clickHA resulted in an increase of the Young's modulus, the compressive strength and, especially, the electrochemical activity. The biocompatibility and the potential for skin regeneration of clickHA/PEDOT-MeOH were preliminary assessed using viability and wound-healing assays with epithelial cells. Not only is the conducting hydrogel formulation biocompatible, but also promotes efficient cell migration by electrostimulation using a small voltage (0.5 V) for a short time (15 min). Thus, in just 1 h the wound gap was repaired, and a homogeneous monolayer of migrated cells was formed.

Preparation and in vitro evaluation of pH and glutathione dual-responsive drug delivery system based on sodium carboxymethyl cellulose

Stimuli-responsive drug delivery systems based on sodium carboxymethyl cellulose (NaCMC) for drug release encounter inherent challenges. In this research, a novel pH and glutathione (GSH) dual-responsive system, CPT-S-S-NaCMC@ZIF-8/SP-PEG, was constructed. Firstly, the prodrug CPT-S-S-OH was synthesized and combined with NaCMC to form GSH-responsive micelles CPT-S-S-NaCMC, significantly enhancing the drug loading and grafting rates to 63.79 % and 91.99 %, respectively. Subsequently, zinc ions and dimethylimidazole can be assembled into porous materials (ZIF-8) on the surface of the micelles. This system exhibits dual pH-GSH responsiveness and effectively reduces the drug release from 84.76 % to 28.71 % at pH = 7.4. Moreover, incorporating pH-responsive spiropyran (SP)-modified polyethylene glycol (PEG) can reduce drug leakage to 16.09 % at pH = 7.4 and exhibit good fluorescence intensity at 722 nm.

Synthesis of Antifouling Poly(ethylene glycol) Brushes via "Grafting to" Approach for Improved Biodistribution.

Polyethylene glycol (PEG) modification of materials has been identified to mitigate the challenge of biofouling. However, the practical application of PEGylation has been hampered by a low PEGylation density on the material surface. Therefore, developing efficient strategies to promote the PEGylation density is crucial. In this study, PEG brushes (PBs) with various structures were synthesized and their physicochemical properties and biomedical applications were investigated. Compared to benzaldehyde (BA), o-phthalaldehyde (OPA) exhibited higher reactivity with amine groups, resulting in increased grafting density (as high as 96.3%) and improved antifouling properties of PEG brushes. Bottlebrushes fabricated by PEG-OPA and polylysine demonstrated a prolonged circulation time in blood and enhanced potential for magnetic resonance imaging of tumors. Furthermore, the rigidity of the backbone was found to be crucial for the antifouling properties of PEG brushes both in vitro and in vivo. These findings are significant and provide valuable insights into designing biomaterials with superior antifouling performance.

Enhancing impact resistance in E‐glass fabric composites through shear thickening fluids and functionalized polyethylene glycol

AbstractIn this study, we delved into innovative strategies to make neat E‐glass fabrics (NGFs) more impact‐ and tensile‐resistant by using shear‐thickening fluids (STFs). To achieve this goal, the polyethylene glycol (PEG) in STFs has been modified. Subsequently, the STF‐impregnated fabric composites were prepared from unmodified PEG and functionally modified PEGs using malonic and tartaric acids, V/S/GF, M/S/GF, and T/S/GF composites, respectively. Fourier‐transform infrared spectroscopy (FTIR) analysis was conducted to confirm the chemical modification of PEGs. The rheological tests showed a significant improvement in the peak viscosity of modified STFs compared with virgin STF. Dynamic rheological analysis also studied media‐particle interaction, revealing improved media‐particle interaction in STFs due to abundant H‐bonding. In addition, a series of experimental tests, namely compressive impact resistance and strip tensile strength tests, have been conducted to investigate the effect of STF modification on the NGF. The results revealed notable improvements in tensile strength and energy dissipation in the T/S/GF and M/S/GF composites compared with V/S/GF and NGF. Importantly, this improvement extended to the impact performance of single, triple, and quintuple layers. Notably, we found that the peak load of 5 T/S/GF was 37.71%, 18.57%, and 11.87% lower than that of 5NGF, 5 V/S/GF, and 5 M/S/GF, respectively. The idea that made these improvements possible came from PEG functionalization, which helps hydrogen bonds form between the dispersed phase and the dispersion medium, leading to higher viscosity. This, in turn, increases inter‐yarn friction, effectively enhancing the spring‐like properties of T/S/GF and M/S/GF compared with V/S/GF. A two‐step artificial intelligence regression analysis underpinned these findings, elucidating the interplay of molecular mechanisms in high‐performance fabric composites.

Synthesis and characterization of antibacterial and low‐temperature resistant slow rebound polyurethane foams

AbstractSlow rebound polyurethane foam (SPUF) has been widely used due to its advantages such as sound insulation, energy absorption, and good tactile sensation. However, SPUF is prone to harden at low temperature, and its application in medical equipment and households requires significant antibacterial properties. In this paper, self‐made silicone modified polyethylene glycol (Si‐APEG) and graphene oxide supported allicin (Alc@GO) were prepared and used as low‐temperature resistant agent and antibacterial agent, respectively. Low‐temperature resistant polyurethane foam (LSPUF) and antibacterial LSPUF (ALSPUF) were prepared respectively with water as foaming agent. The morphology of ALSPUF was observed by scanning electron microscope. Properties studied include apparent core density and porosity, mechanical properties including tensile strength, 40% compressive hardness, and rebound resilience, as well as low‐temperature resistance. Effects of Si‐APEG content on the structures and properties were analyzed and the LSPUF with an Si‐APEG content of 10 wt.% showed the best comprehensive performance. Therefore, ALSPUFs with Si‐APEG content of 10 wt.% and Alc@GO content of 0–3 wt.% were prepared. The addition of Alc@GO increased the antibacterial ratio significantly without obvious effect on the structure and mechanical properties of LSPUF. The antibacterial ratio of ALSPUF reached 99.07% at a Alc@GO content of 2.5 wt.% and testing time of 60 min. This work provides an effective and feasible method for the preparation of ALSPUF which can be widely used in medical devices and households.Highlights Silicone modified polyether is a suitable low‐temperature resistant agent for PU foam. Allicin supported on GO provides good antibacterial property for PU foam. ALSPUF has better mechanical properties than SPU.

Development of an in-situ forming collagen-based hydrogel as a regenerative bioadhesive for corneal perforations

Corneal injuries play a significant role in global visual impairment, underscoring the demand for innovative biomaterials with specific attributes such as adhesion, cohesion, and regenerative potential. In this study, we have developed a biocompatible bioadhesive for corneal reconstruction. Derived from Collagen type I, naturally present in human corneal stromal tissue, the bioadhesive was cross-linked with modified polyethylene glycol diacrylate (PEGDA-DOPA), rendering it curable through visible light exposure and exhibiting superior adhesion to biological tissues even in wet conditions. The physicochemical characteristics of the proposed bioadhesive were customized by manipulating the concentration of its precursor polymers and adjusting the duration of photocrosslinking. To identify the optimal sample with maximum adhesion, mechanical strength, and biocompatibility, characterization tests were conducted. The optimal specimen, consisting of 30 % (w/v) PEGDA-DOPA and cured with visible light for 5 min, exhibited commendable adhesive strength of 783.6 kPa and shear strength of 53.7 kPa, surpassing that of commercialized eye adhesives.Additionally, biocompatibility test results indicated a notably high survival rate (>100 %) of keratocytes seeded on the hydrogel adhesive after 7 days of incubation. Consequently, this designed bioadhesive, characterized by high adhesion strength, robust mechanical strength, and excellent biocompatibility, is anticipated to enhance the spontaneous repair process of damaged corneal stromal tissue.

Chemical engineering of zein with polyethylene glycol and Angiopep-2 to manufacture a brain-targeted docetaxel nanomedicine for glioblastoma treatment.

Glioblastoma (GBM) is the deadliest adult brain cancer. The current standard-of-care chemotherapy using orally administered temozolomide (TMZ) presents poor improvement in patient survival, emphasizing the compelling need for new therapies. A possible chemotherapeutic alternative is docetaxel (DTX), which possesses higher tumoricidal potency against GBM cells. However, its limited blood-brain barrier (BBB) permeability poses a constraint on its application. Nonetheless, nanomedicine offers promising avenues for overcoming this challenge. Angiopep-2 (ANG2) is a peptide that targets the BBB-overexpressed low-density lipoprotein receptor (LDLR). In this work, we managed, for the first time, to employ a pioneering approach of covalently linking zein protein with polyethylene glycol (PEG) and ANG2 prior to its formulation into nanoparticles (ZNPs) with enhanced stability and LDLR-mediated brain targetability, respectively. Carbodiimide and click chemistry approaches were optimized, resulting in functional modification of zein with around 25% PEG, followed by functional modification of PEG with nearly 100% ANG2. DTX-loaded ZNPs presented 100nm average size, indicating high suitability for BBB crossing through receptor-mediated transcytosis. ZNPs maintained the cytotoxic effect of the loaded DTX against GBM cells, while demonstrating a safe matrix against BBB cells. Importantly, these brain-targeted ZNPs showcased up to fourfold enhancement in blood-to-brain permeability in a BBB in vitro model, highlighting the potential of this novel approach of BBB targeting in significantly improving therapeutic outcomes for GBM patients. The versatility of the system and the possibility of significantly increasing drug concentration in the brain open the door to its future application in a wide range of other brain-related diseases.

Co-delivery of retinoic acid and miRNA by functional Au nanoparticles for improved survival and CT imaging tracking of MSCs in pulmonary fibrosis therapy

Mesenchymal stem cells (MSCs) have emerged as promising candidates for idiopathic pulmonary fibrosis (IPF) therapy. Increasing the MSC survival rate and deepening the understanding of the behavior of transplanted MSCs are of great significance for improving the efficacy of MSC-based IPF treatment. Therefore, dual-functional Au-based nanoparticles (Au@PEG@PEI@TAT NPs, AuPPT) were fabricated by sequential modification of cationic polymer polyetherimide (PEI), polyethylene glycol (PEG), and transactivator of transcription (TAT) penetration peptide on AuNPs, to co-deliver retinoic acid (RA) and microRNA (miRNA) for simultaneously enhancing MSC survive and real-time imaging tracking of MSCs during IPF treatment. AuPPT NPs, with good drug loading and cellular uptake abilities, could efficiently deliver miRNA and RA to protect MSCs from reactive oxygen species and reduce their expression of apoptosis executive protein Caspase 3, thus prolonging the survival time of MSC after transplantation. In the meantime, the intracellular accumulation of AuPPT NPs enhanced the computed tomography imaging contrast of transplanted MSCs, allowing them to be visually tracked in vivo. This study establishes an Au-based dual-functional platform for drug delivery and cell imaging tracking, which provides a new strategy for MSC-related IPF therapy.

Enhancing camptothecin loading and release control through physical surface modification of organosilica nanoparticles with polyethylene glycol

The surface modification of nanoparticles holds the potential to enhance the loading capacity of drug molecules and regulate their release, making it possible to exploit the differences between tumor and normal cells. To this end, the surfaces of tetrasulfide-based phenylene-containing biodegradable periodic mesoporous organosilica (BPMO) nanoparticles (designated P4S) are modified herein with a hydrophilic and biocompatible polyethylene glycol (PEG) polymer. The PEG coating is optimized by adjusting the PEG concentration during synthesis, thus resulting in a significant increase in the nanoparticle stability. Furthermore, PEG modification enhances the nanoparticles' camptothecin (CPT) loading capacity. Drug release assessments under physical and acidic pH conditions demonstrate the pH-responsive properties of the P4S nanoparticles upon PEG functionalization, which results in increased drug release at low pH, along with enhanced cellular uptake potential. Notably, the cytotoxicity of CPT against HepG2 cancer cells is significantly improved when loaded into the P4S-PEG nanoparticles. These findings reveal the efficacy of PEG surface modification of the drug-delivery material in augmenting the activity of CPT, with promising prospects for clinical applications.

A Concise Review on Effect of PEGylation on the Properties of Lipid-Based Nanoparticles.

Nanoparticle-based drug delivery systems have emerged as promising platforms for enhancing therapeutic efficacy while minimizing off-target effects. Among various strategies employed to optimize these systems, polyethylene glycol (PEG) modification, known as PEGylation-the covalent attachment of PEG to nanoparticles, has gained considerable attention for its ability to impart stealth properties to nanoparticles while also extending circulation time and improving biocompatibility. PEGylation extends to different drug delivery systems, in specific, nanoparticles for targeting cancer cells, where the concentration of drug in the cancer cells is improved by virtue of PEGylation. The primary challenge linked to PEGylation lies in its confirmation. Numerous research findings provide comprehensive insights into selecting PEG for various PEGylation methods. In this review, we have endeavored to consolidate the outcomes concerning the choice of PEG and diverse PEGylation techniques.

Melittin-loaded gold nanocages camouflaged by anti-MUC18 functionalized lipid bilayers for chemo-photothermal ablation of melanoma cells

Melittin (MEL), a potent apoptotic substance, holds promise for cancer treatment. However, due to its undesirable side, its direct use in humans is limited. On the other hand, gold nanocages (AuNCs) have gained attention as potential nanocarriers for cancer therapy due to their high loading capacity and photothermal effect. In this study, a targeted MEL-based delivery system in melanoma was developed by post-inserting anti-MUC18 single-chain antibodies modified polyethylene glycol (PEG)-lipid onto AuNCs, resulting in Immuno-liposomal layer modified AuNCs (AuNC@scFv-lip) with a hydrodynamic size of approximately 96 nm. The negatively charged surface of AuNCs allowed for a high loading efficiency of 93 % for MEL. MEL-loaded AuNCs@scFv-lip (MEL-AuNCs@scFv-lip) demonstrated dual acidic pH and near-infrared (NIR) irradiation-triggered release. Cellular internalization of AuNC@scFv-lip were investigated in A375 melanoma cells using flow cytometry, showing an approximately 18-fold higher cellular uptake compared to non-targeted liposomal layer modified AuNCs (AuNC@lip). Additionally, AuNC@scFv-lip was internalized via clathrin-dependent endocytosis, while AuNC@lip primarily utilized the caveolae-dependent pathway. MEL-AuNC@scFv-lip exhibited increased toxicity toward A375 cells compared to MEL-AuNC@lip. Moreover, the IC50 of MEL-AuNC@scFv-lip decreased in the presence of laser irradiation, combining MEL's cytotoxic effect with photothermal ablation of A375 cells. Overall, this multifunctional targeted nanocarrier possesses key structural characteristics, making it a promising candidate for remote-controlled combination therapy of melanoma.

Impact of protein corona and PEGylation on the accumulation and efficacy of lysosome-disrupting lipid nanoparticles in KRAS-mutated cancer

Nanomedicines offer promising approaches for targeted drug delivery to tumor cells but their clinical translation is hindered by limited delivery efficacy in heterogenous clinical tumors. Protein corona adsorbed to the surface of nanoparticles (NPs) would cause opsonization and accelerate blood clearance, posing a significant barrier to effective drug delivery. Polyethylene glycol (PEG) modification is widely employed to prolong the NPs’ circulation time and improve the delivery efficacy. Nevertheless, the clinical efficacy of PEG-based nanomedicines is still debatable. Here, we prepared non-PEGylated lysosomal-disrupting dimeric chloroquine (CQ) lipid nanoparticles (DCLNPs) and PEGylated DCLNPs (PEG-DCLNPs) and systematically studied the impact of PEGylation on DCLNPs’ delivery efficacy in KRAS-mutant (MT) and -wildtype (WT) cancers. We found that the protein corona facilitates KRAS-MT cancer-specific targeted delivery of DCLNPs by exploiting extracellular protein engulfment preference. In contrast, PEGylation hindered delivery and efficacy of DCLNPs. Proteomics analysis highlighted apolipoproteins, particular apolipoprotein E, as key factors promoting the uptake of DCLNPs. Additionally, DCLNPs sensitized immunosuppressive KRAS-MT cancers to anti-PD1 immunotherapy. These results underscore the importance of comprehending the context-dependent role of the protein corona in regulating nanoparticle biodistribution, suggesting that PEGylation may not be suitable across all cancer types.

PEG modification increases thermostability and inhibitor resistance of Bst DNA polymerase.

Polyethylene glycol modification (PEGylation) is a widely used strategy to improve the physicochemical properties of various macromolecules, especially protein drugs. However, its application in enhancing the performance of enzymes for molecular biology remains underexplored. This study explored the PEGylation of Bst DNA polymerase, determining optimal modification reaction conditions. In comparison to the unmodified wild-type counterpart, the modified Bst DNA polymerase exhibited significantly improved activity, thermal stability, and inhibitor tolerance during loop-mediated isothermal amplification. When applied for the detection of Salmonella in crude samples, the modified enzyme demonstrated a notably accelerated reaction rate. Therefore, PEGylation emerges as a viable strategy for refining DNA polymerases, helping in the development of novel molecular diagnostic reagents.

Combined ROS Sensitive Folate Receptor Targeted Micellar Formulations of Curcumin Effective Against Rheumatoid Arthritis in Rat Model.

Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that involves synovitis, cartilage destruction, and even joint damage. Traditional agents used for RA therapy remain unsatisfactory because of their low efficiency and obvious adverse effects. Therefore, we here established RA microenvironment-responsive targeted micelles that can respond to the increase in reactive oxygen species (ROS) levels in the joint and improve macrophage-specific targeting of loaded drugs. We here prepared ROS-responsive folate-modified curcumin micelles (TK-FA-Cur-Ms) in which thioketal (TK) was used as a ROS-responsive linker for modifying polyethylene glycol 5000 (PEG5000) on the micellar surface. When micelles were in the ROS-overexpressing inflammatory microenvironment, the PEG5000 hydration layer was shed, and the targeting ligand FA was exposed, thereby enhancing cellular uptake by macrophages through active targeting. The targeting, ROS sensitivity and anti-inflammatory properties of the micelles were assessed in vitro. Collagen-induced arthritis (CIA) rats model was utilized to investigate the targeting, expression of serum inflammatory factors and histology change of the articular cartilage by micelles in vivo. TK-FA-Cur-Ms had a particle size of 90.07 ± 3.44 nm, which decreased to 78.87 ± 2.41 nm after incubation with H2O2. The micelles exhibited in vitro targeting of RAW264.7 cells and significantly inhibited inflammatory cytokine levels. Pharmacodynamic studies have revealed that TK-FA-Cur-Ms prolonged the drug circulation and exhibited augmented cartilage-protective and anti-inflammatory effects in vivo. The unique ROS-responsive targeted micelles with targeting, ROS sensitivity and anti-inflammatory properties were successfully prepared and may offer an effective therapeutic strategy against RA.