A highly sensitive electrochemical sensor based on poly(3-aminobenzoic acid)/graphene oxide-gold nanoparticles modified screen printed carbon electrode for paraquat detection.

Herein, a modified screen printed carbon electrode (SPCE) based on a composite material, graphene oxide-gold nanoparticles (GO-AuNPs), and poly(3-aminobenzoic acid)(P3ABA) for the detection of paraquat (PQ) is introduced. The modified electrode was fabricated by drop casting of the GO-AuNPs, followed by electropolymerization of 3-aminobenzoic acid to achieve SPCE/GO-AuNPs/P3ABA. The morphology and microstructural characteristics of the modified electrodes were revealed by scanning electron microscopy (SEM) for each step of modification. The composite GO-AuNPs can provide high surface area and enhance electroconductivity of the electrode. In addition, the presence of negatively charged P3ABA notably improved PQ adsorption and electron transfer rate, which stimulate redox reaction on the modified electrode, thus improving the sensitivity of PQ analysis. The SPCE/GO-AuNPs/P3ABA offered a wide linear range of PQ determination (10-9-10-4 mol/L) and low limit of detection (LOD) of 0.45 × 10-9 mol/L or 0.116 µg/L, which is far below international safety regulations. The modified electrode showed minimum interference effect with percent recovery ranging from 96.5% to 116.1% after addition of other herbicides, pesticides, metal ions, and additives. The stability of the SPCE/GO-AuNPs/P3ABA was evaluated, and the results indicated negligible changes in the detection signal over 9 weeks. Moreover, this modified electrode was successfully implemented for PQ analysis in both natural and tapped water with high accuracy.

Targeted polymeric primaquine nanoparticles: optimization, evaluation, and in-vivo liver uptake for improved malaria treatment.

Primaquine (PQ) is a widely used antimalarial drug, but its high dosage requirements can lead to significant tissue damage and adverse gastrointestinal and hematological effects. Recent studies have shown that nanoformulations can enhance the bioavailability of pharmaceuticals, thereby increasing efficacy, reducing dosing frequency, and minimizing toxicity. In this study, PQ-loaded PLGA nanoparticles (PQ-NPs) were prepared using a modified double emulsion solvent evaporation technique (w/o/w). The PQ-NPs exhibited a mean particle size of 228 ± 2.6 nm, a zeta potential of +27.4 mV, and an encapsulation efficiency of 81.3 ± 3.5%. Scanning electron microscopy (SEM) confirmed their spherical morphology, and the in vitro release profile demonstrated continuous drug release over 72 h. Differential scanning calorimetry (DSC) thermograms indicated that the drug was present in the nanoparticles, with improved physical stability. Fourier-transform infrared spectroscopy (FTIR) analysis showed no interactions between the various substances in the NPs. In vivo studies in Swiss albino mice infected with Plasmodium berghei revealed that the nanoformulated PQ was 20% more effective than the standard oral dose. Biodistribution studies indicated that 80% of the NPs accumulated in the liver, highlighting their potential for targeted drug delivery. This research demonstrates the successful development of a nanomedicine delivery system for antimalarial drugs, offering a promising strategy to enhance treatment efficacy while reducing adverse effects.

Air-microwave simultaneously induced carbon fiber surface oxidation and magnetism adjustment by CoOx nanoparticles rapid assembly for interface enhancement and electromagnetic wave absorption of its composites.

It is a significant challenge to develop a fast carbon fiber (CF) surface modification method, especially for the high strength electromagnetic wave (EMW) absorption materials. Herein, magnetic CoOx nanoparticles are successfully synthesized and uniformly assembled on CF surface with high oxygen-containing groups by rapid ambient microwave carbon thermal shock (MCTS). The presence of oxygen defect sites on CF surface promotes CoOx nanoparticles nucleation. The number of oxygen defects and the types of magnetic nanoparticles on the CF surface effectively adjust the surface chemical activity and the electromagnetic properties of CF, which is conducive to improving the EMW absorption performance and interface compatibility of the CoOx nanoparticles modified CF reinforced polyamide 6 (CO@CF/PA6) composites. Compared with CO@CF-0 s/PA6, the tensile strength and modulus of CO@CF-3.5 s/PA6 composite are increased by 18.1 % and 18.6 %, respectively. It also displays a minimum reflection loss value (-59.9 dB) at a thinner thickness of 1.9 mm while the maximum effective absorption bandwidth reaches 5.02 GHz with a thickness of 1.8 mm. Its radar cross-section values exhibit less than -10 dBm2 at all tested detection angles. This rapid MCTS shows great potential for large-scale production of CF modification with low-cost, efficient and environmentally friendly process.

Ligand-free biodegradable poly(beta-amino ester) nanoparticles for targeted systemic delivery of mRNA to the lungs.

Non-viral nanoparticles (NPs) have seen heightened interest as a delivery method for a variety of clinically relevant nucleic acid cargoes in recent years. While much of the focus has been on lipid NPs, non-lipid NPs, including polymeric NPs, have the possibility of improved efficacy, safety, and targeting, especially to non-liver organs following systemic administration. A safe and effective systemic approach for intracellular delivery to the lungs could overcome limitations to intratracheal/intranasal delivery of NPs and improve clinical benefit for a range of diseases including cystic fibrosis. Here, engineered biodegradable poly (beta-amino ester) (PBAE) NPs are shown to facilitate efficient delivery of mRNA to primary human airway epithelial cells from both healthy donors and individuals with cystic fibrosis. Optimized NP formulations made with differentially endcapped PBAEs and systemically administered in vivo lead to high expression of mRNA within the lungs in BALB/c and C57 B/L mice without requiring a complex targeting ligand. High levels of mRNA-based gene editing were achieved in an Ai9 mouse model across bronchial, epithelial, and endothelial cell populations. No toxicity was observed either acutely or over time, including after multiple systemic administrations of the NPs. The non-lipid biodegradable PBAE NPs demonstrate high levels of transfection in both primary human airway epithelial cells and in vivo editing of lung cell types that are targets for numerous life-limiting diseases particularly single gene disorders such as cystic fibrosis and surfactant deficiencies.

Enhancing bone regeneration: Unleashing the potential of magnetic nanoparticles in a microtissue model.

Bone tissue engineering addresses the limitations of autologous resources and the risk of allograft disease transmission in bone diseases. In this regard, engineered three-dimensional (3D) models emerge as biomimetic alternatives to natural tissues, replicating intracellular communication. Moreover, the unique properties of super-paramagnetic iron oxide nanoparticles (SPIONs) were shown to promote bone regeneration via enhanced osteogenesis and angiogenesis in bone models. This study aimed to investigate the effects of SPION on both osteogenesis and angiogenesis and characterized a co-culture of Human umbilical vein endothelial cells (HUVEC) and MG-63 cells as a model of bone microtissue. HUVECs: MG-63s with a ratio of 4:1 demonstrated the best results among other cell ratios, and 50 µg/mL of SPION was the optimum concentration for maximum survival, cell migration and mineralization. In addition, the data from gene expression illustrated that the expression of osteogenesis-related genes, including osteopontin, osteocalcin, alkaline phosphatase, and collagen-I, as well as the expression of the angiogenesis-related marker, CD-31, and the tube formation, is significantly elevated when the 50 µg/mL concentration of SPION is applied to the microtissue samples. SPION application in a designed 3D bone microtissue model involving a co-culture of osteoblast and endothelial cells resulted in increased expression of specific markers related to angiogenesis and osteogenesis. This includes the design of a novel biomimetic model to boost blood compatibility and biocompatibility of primary materials while promoting osteogenic activity in microtissue bone models. Moreover, this can improve interaction with surrounding tissues and broaden the knowledge to promote superior-performance implants, preventing device failure.

Bcl-2 knockdown by multifunctional lipid nanoparticle and its influence in apoptosis pathway regarding cutaneous melanoma: in vitro and ex vivo studies.

Multifunctional therapies have emerged as innovative strategies in cancer treatment. In this research article, we proposed a nanostructured lipid carrier (NLC) designed for the topical treatment of cutaneous melanoma, which simultaneously delivers 5-FU and Bcl-2 siRNA. The characterized nanoparticles exhibited a diameter of 259 ± 9 nm and a polydispersion index of 0.2, indicating a uniform size distribution. The NLCs were primarily localized in the epidermis, effectively minimizing the systemic release of 5-FU across skin layers. The ex vivo skin model revealed the formation of a protective lipid film, decreasing the desquamation process of the stratum corneum which can be associated to an effect of increasing permeation. In vitro assays demonstrated that A375 melanoma cells exhibited a higher sensitivity to the treatment compared to non-cancerous cells, reflecting the expected difference in their metabolic rates. The uptake of NLC by A375 cells reached approximately 90% within 4 h. The efficacy of Bcl-2 knockdown was thoroughly assessed using ELISA, Western blot, and qRT-PCR analyses, revealing a significant knockdown and synergistic action of the NLC formulation containing 5-FU and Bcl-2 siRNA (at low concentration --100 pM). Notably, the silencing of Bcl-2 mRNA also impacted other members of the Bcl-2 protein family, including Mcl-1, Bcl-xl, BAX, and BAK. The observed modulation of these proteins strongly indicated the activation of the apoptosis pathway, suggesting a successful inhibition of melanoma growth and prevention of its in vitro spread.

Temporal and spatial resolution of magnetosome degradation at the subcellular level in a 3D lung carcinoma model.

Magnetic nanoparticles offer many exciting possibilities in biomedicine, from cell imaging to cancer treatment. One of the currently researched nanoparticles are magnetosomes, magnetite nanoparticles of high chemical purity synthesized by magnetotactic bacteria. Despite their therapeutic potential, very little is known about their degradation in human cells, and even less so of their degradation within tumours. In an effort to explore the potential of magnetosomes for cancer treatment, we have explored their degradation process in a 3D human lung carcinoma model at the subcellular level and with nanometre scale resolution. We have used state of the art hard X-ray probes (nano-XANES and nano-XRF), which allow for identification of distinct iron phases in each region of the cell. Our results reveal the progression of magnetite oxidation to maghemite within magnetosomes, and the biosynthesis of magnetite and ferrihydrite by ferritin.

Emerging Nanotherapeutic Approaches for Diabetic Wound Healing.

Diabetic wounds pose a significant challenge in modern healthcare due to their chronic and complex nature, often resulting in delayed healing, infections, and, in severe cases, amputations. In recent years, nanotherapeutic approaches have emerged as promising strategies to address the unique pathophysiological characteristics of diabetic wounds. This review paper provides a comprehensive overview of the latest advancements in nanotherapeutics for diabetic wound treatment. We discuss various nanomaterials and delivery systems employed in these emerging therapies. Furthermore, we explore the integration of biomaterials to enhance the efficacy of nanotherapeutic interventions. By examining the current state-of-the-art research, challenges, and prospects, this review aims to offer valuable insights for researchers, clinicians, and healthcare professionals working in the field of diabetic wound care.

Nanoparticles as a Novel Platform for Cardiovascular Disease Diagnosis and Therapy.

Cardiovascular disease (CVD) is a major global health issue with high mortality and morbidity rates. With the advances in nanotechnology, nanoparticles are receiving increasing attention in diagnosing and treating CVD. Previous studies have explored the use of nanoparticles in noninvasive diagnostic technologies, such as magnetic resonance imaging and computed tomography. Nanoparticles have been extensively studied as drug carriers and prognostic factors, demonstrating synergistic efficacy. This review summarized the current applications of nanoparticles in CVD and discussed their opportunities and challenges for further exploration.

Delivery of a STING Agonist Using Lipid Nanoparticles Inhibits Pancreatic Cancer Growth.

Introduction: The tumor microenvironment (TME) of pancreatic cancer is highly immunosuppressive and characterized by a large number of cancer-associated fibroblasts, myeloid-derived suppressor cells, and regulatory T cells. Stimulator of interferon genes (STING) is an endoplasmic reticulum receptor that plays a critical role in immunity. STING agonists have demonstrated the ability to inflame the TME, reduce tumor burden, and confer anti-tumor activity in mouse models. 2'3' cyclic guanosine monophosphate adenosine monophosphate (2'3'-cGAMP) is a high-affinity endogenous ligand of STING. However, delivering cGAMP to antigen-presenting cells and tumor cells within the cytosol remains challenging due to membrane impermeability and poor stability. Methods: In this study, we encapsulated 2'3'-cGAMP in a lipid nanoparticle (cGAMP-LNP) designed for efficient cellular delivery. We assessed the properties of the nanoparticles using a series of in-vitro studies designed to evaluate their cellular uptake, cytosolic release, and minimal cytotoxicity. Furthermore, we examined the nanoparticle's anti-tumor effect in a syngeneic mouse model of pancreatic cancer. Results: The lipid platform significantly increased the cellular uptake of 2'3'-cGAMP. cGAMP-LNP exhibited promising antitumor activity in the syngeneic mouse model of pancreatic cancer. Discussion: The LNP platform shows promise for delivering exogenous 2'3'-cGAMP or its derivatives in cancer therapy.

Remote-controlled dexamethasone-duration on eye-surface with a micelle-magnetic nanoparticulate co-delivery system for dry eye disease.

Dexamethasone (DEX) is used to treat ocular surface diseases. However, regulating DEX duration in tears while preventing its absorption into the anterior chamber is critical for balancing its therapy effects and the side effects. In this study, a novel magnetic nanoparticle (MNP)-micelle (MC) co-delivery system (MMDS) was developed. The MC moiety in the MMDS served as the carrier for DEX and the MNP part endowed the MMDS with magnetic-responsive properties. To extend its residency, the MMDS was magnetically attracted by an external magnet after instilling, which acted as a precorneal drug-depot enabling a sustainable release of DEX in tears. With combination of magnet treatment, the topical instillation of MMDS@DEX significantly prolonged the DEX-retention in tears and increased the DEX-concentration in the cornea and conjunctiva, as well as concurrently reduced the DEX-level in the aqueous humor, when compared with the commercial DEX eye drop treatment. The combination of MMDS@DEX and magnet treatment exerted significantly better therapeutic effects against DED with smaller side effects than conventional treatments including DEX suspension, commercial DEX eye drops, as well as the MMDS@DEX treatment alone. The present work provided a new method for the effective delivery of DEX to ocular surface tissues while reducing its side effects, which will be beneficial to the treatments of a wide range of ocular surface diseases.

Effects of nanoparticle deformability on multiscale biotransport.

Deformability is one of the critical attributes of nanoparticle (NP) drug carriers, along with size, shape, and surface properties. It affects various aspects of NP biotransport, ranging from circulation and biodistribution to interactions with biological barriers and target cells. Recent studies report additional roles of NP deformability in biotransport processes, including protein corona formation, intracellular trafficking, and organelle distribution. This review focuses on the literature published in the past five years to update our understanding of NP deformability and its effect on NP biotransport. We introduce different methods of modulating and evaluating NP deformability and showcase recent studies that compare a series of NPs in their performance in biotransport events at all levels, highlighting the consensus and disagreement of the findings. It concludes with a perspective on the intricacy of systematic investigation of NP deformability and future opportunities to advance its control toward optimal drug delivery.

cRGD-platelet@MnO/MSN@PPARα/LXRα Nanoparticles Improve Atherosclerosis in Rats by Inhibiting Inflammation and Reducing Blood Lipid.

OBJECTIVE: Atherosclerosis (AS) is an inflammatory disease of arterial intima driven by lipids. Liver X receptor alpha (LXRα) and peroxisome proliferator-activated receptor alpha (PPARα) agonists are limited in the treatment of AS due to their off-target effects and serious side effects. Therefore, this study was designed to construct a novel nanoparticle (NP) and evaluate its mechanism of action on inflammation inhibition and lipid reduction in AS. METHODS: We synthesized cRGD-platelet@MnO/MSN@PPARα/LXRα NPs (cRGD-platelet- NPs) and confirmed their size, safety, and targeting ability through various tests, including dynamic light scattering and immunofluorescence. In vivo and in vitro experiments assessed cell proliferation, apoptosis, inflammation, and plaque formation. Finally, the NF-κB signaling pathway expression in rat aorta was determined using a western blot. RESULTS: The synthesis of cRGD-platelet-NPs was successful; the particle size was approximately 150 nm, and the PDI was below 0.3. They could be successfully absorbed by cells, exhibiting high safety in vivo and in vitro. The cRGD-platelet-NPs successfully reduced plaque formation, improved lipid profiles by lowering LDL-cholesterol, total cholesterol, and triglycerides, and raised HDL-cholesterol levels. Additionally, they decreased inflammatory markers in the serum and aortic tissue, suggesting reduced inflammation. Immunohistochemistry and western blot analyses indicated that these NPs could not only promote M2 macrophage polarization but also suppress the NF-κB signaling pathway. CONCLUSION: The newly developed cRGD-platelet-NPs with high safety are a promising approach to AS treatment, which can regulate ABCA1, reduce the formation of AS plaques, and enhance cholesterol efflux. The mechanism may involve the suppression of the NF-κB signaling pathway.

Nanoscale dosimetry for a radioisotope-labeled metal nanoparticle using MCNP6.2 and Geant4.

BACKGROUND: Metal nanoparticles (MNPs) labeled with radioisotopes (RIs) are utilized as radio-enhancers due to their ability to amplify the radiation dose in their immediate vicinity. A thorough understanding of nanoscale dosimetry around MNPs enables their effective application in radiotherapy. However, nanoscale dosimetry around MNPs still requires further investigation. PURPOSE: This study aims to provide insight into the radio-enhancement effects of MNPs by elucidating nanoscale dosimetry surrounding MNPs labeled with Auger-emitting RIs. We particularly focus on distinguishing the respective dose contributions of photons and electrons emitted by Auger-emitting RIs in the context of dose enhancement. METHODS: A 50 nm diameter NP of silver (Ag) core and gold (Au) shell (Ag@Au NP) was assumed to emit mono-energetic electrons and photons (3, 5, 10, 20, and 30 keV), or the energy spectrum corresponding to one of three Auger-emitting RIs (103Pd, 125I, and 131Cs) from the Ag core. Nanoscale radial dose distributions around a single radioactive Ag@Au NP were evaluated in spherical shells of water. Monte Carlo simulations were conducted using single-event and track structure transport methods implemented in MCNP6.2 and Geant4-DNA-Au physics, respectively. To evaluate the extent of radio-enhancement by the Ag@Au NP, two scenarios were considered: Ag@Au NPs (Au shell included) and Ag@water NPs (Au shell replaced by water). RESULTS: The radial doses of 10, 20, and 30 keV electrons estimated by both codes were comparable. However, the radial doses of 3 and 5 keV electrons by MCNP6.2 were much larger near the NP surface than those by Geant4. There was a dose enhancement of a few % to tens % by the Au shell in the region of the NP surface to 10 µm, depending on the electron energy. The radial doses of photons with the Au shell were higher up to their secondary electron ranges than those without the Au shell. The maximum dose enhancement factor of photons occurred at 20 keV and was 63.4 by MCNP6.2 and 50.5 by Geant4. The overall radial doses of electrons were 1-2 orders of magnitude larger than those of photons. As a result, in cases of RIs emitting both electrons and photons, the radial doses up to electron ranges were dominantly governed by electrons. The dose enhancement estimated by both codes for the RIs ranged from a few % except in the immediate vicinity of the NP surface. CONCLUSION: Given the dominant contribution of electrons to radial doses of MNP labeled with Auger-emitting RIs, physical dose enhancement expected by interactions with photons was hindered. Since there are no available RIs emitting exclusively photons, achieving enhanced physical doses within a cell through a combination of MNPs and RIs appears currently unattainable. The radial doses of photons near the NP surface exhibited considerable discrepancies between the codes, primarily attributed to low-energy electrons. The difference may arise from higher cross-sections of Au inelastic scattering in Geant4-DNA-Au compared to MCNP6.2.

Biophysical translational paradigm of polymeric nanoparticle: Embarked advancement to brain tumor therapy.

Polymeric nanoparticles have emerged as promising contenders for addressing the intricate challenges encountered in brain tumor therapy due to their distinctive attributes, including adjustable size, biocompatibility, and controlled drug release kinetics. This review comprehensively delves into the latest developments in synthesizing, characterizing, and applying polymeric nanoparticles explicitly tailored for brain tumor therapy. Various synthesis methodologies, such as emulsion polymerization, nanoprecipitation, and template-assisted fabrication, are scrutinized within the context of brain tumor targeting, elucidating their advantages and limitations concerning traversing the blood-brain barrier. Furthermore, strategies pertaining to surface modification and functionalization are expounded upon to augment the stability, biocompatibility, and targeting prowess of polymeric nanoparticles amidst the intricate milieu of the brain microenvironment. Characterization techniques encompassing dynamic light scattering, transmission electron microscopy, and spectroscopic methods are scrutinized to evaluate the physicochemical attributes of polymeric nanoparticles engineered for brain tumor therapy. Moreover, a comprehensive exploration of the manifold applications of polymeric nanoparticles encompassing drug delivery, gene therapy, imaging, and combination therapies for brain tumours is undertaken. Special emphasis is placed on the encapsulation of diverse therapeutics within polymeric nanoparticles, thereby shielding them from degradation and enabling precise targeting within the brain. Additionally, recent advancements in stimuli-responsive and multifunctional polymeric nanoparticles are probed for their potential in personalized medicine and theranostics tailored for brain tumours. In essence, this review furnishes an all-encompassing overview of the recent strides made in tailoring polymeric nanoparticles for brain tumor therapy, illuminating their synthesis, characterization, and multifaceted application.

Nanoparticles targeting immune checkpoint protein VISTA induce potent antitumor immunity.

BACKGROUND: Immune checkpoint protein V-domain immunoglobulin suppressor of T cell activation (VISTA) controls antitumor immunity and is a valuable target for cancer immunotherapy. Previous mechanistic studies have indicated that VISTA impairs the toll-like receptor (TLR)-mediated activation of myeloid antigen-presenting cells, promoting the expansion of myeloid-derived suppressor cells, and suppressing tumor-reactive cytotoxic T cell function. METHODS: The aim of this study was to develop a dual-action lipid nanoparticle (dual-LNP) coloaded with VISTA-specific siRNA and TLR9 agonist CpG oligonucleotide. We used three murine preclinical tumor models, melanoma YUMM1.7, melanoma B16F10, and colon carcinoma MC38 to assess the functional synergy of the two cargoes of the dual LNP and therapeutic efficacy. RESULTS: The dual-LNP synergistically augmented antitumor immune responses and rejected large established tumors whereas LNPs containing VISTA siRNA or CpG alone were ineffective. In comparison with therapies using the soluble CpG and a VISTA-specific monoclonal antibody, the dual-LNP demonstrated superior therapeutic efficacy yet with reduced systemic inflammatory cytokine production. In three murine models, the dual-LNP treatment achieved a high cure rate. Tumor rejection was associated with influx of immune cells to tumor tissues, augmented dendritic cell activation, production of proinflammatory cytokines, and improved function of cytotoxic T cells. CONCLUSIONS: Our studies show the dual-LNP ensured codelivery of its synergistic cargoes to tumor-infiltrating myeloid cells, leading to simultaneous silencing of VISTA and stimulation of TLR9. As a result, the dual-LNP drove a highly potent antitumor immune response that rejected large aggressive tumors, thus may be a promising therapeutic platform for treating immune-cold tumors.

Biogenically synthesized green silver nanoparticles exhibit antimalarial activity.

The suboptimal efficacies of existing anti-malarial drugs attributed to the emergence of drug resistance dampen the clinical outcomes. Hence, there is a need for developing novel drug and drug targets. Recently silver nanoparticles (AgNPs) constructed with the leaf extracts of Euphorbia cotinifolia were shown to possess antimalarial activity. Therefore, the synthesized AgNPs from Euphorbia cotinifolia (EcAgNPs) were tested for their parasite clearance activity. We determined the antimalarial activity in the asexual blood stage infection of 3D7 (laboratory strain) P. falciparum. EcAgNPs demonstrated the significant inhibition of parasite growth (EC50 of 0.75 µg/ml) in the routine in vitro culture of P. falciparum. The synthesized silver nanoparticles were seen to induce apoptosis in P. falciparum through increased reactive oxygen species (ROS) ROS production and activated programmed cell death pathways characterized by the caspase-3 and calpain activity. Also, altered transcriptional regulation of Bax/Bcl-2 ratio indicated the enhanced apoptosis. Moreover, inhibited expression of PfLPL-1 by EcAgNPs is suggestive of the dysregulated host fatty acid flux via parasite lipid storage. Overall, our findings suggest that EcAgNPs are a non-toxic and targeted antimalarial treatment, and could be a promising therapeutic approach for clearing malaria infection.

Dispersion strategies of nanomaterials in polymeric inks for efficient 3D printing of soft and smart 3D structures: A systematic review.

Nanoscience-often summarized as "the future is tiny"-highlights the work of researchers advancing nanotechnology through incremental innovations. The design and innovation of new nanomaterials are vital for the development of next-generation three-dimensional (3D) printed structures characterized by low cost, high speed, and versatile capabilities, delivering exceptional performance in advanced applications. The integration of nanofillers into polymeric-based inks for 3D printing heralds a new era in additive manufacturing, allowing for the creation of custom-designed 3D objects with enhanced multifunctionality. To optimize the use of nanomaterials in 3D printing, effective disaggregation techniques and strong interfacial adhesion between nanofillers and polymer matrices are essential. This review provides an overview of the application of various types of nanomaterials used in 3D printing, focusing on their functionalization principles, dispersion strategies, and colloidal stability, as well as the methodologies for aligning nanofillers within the 3D printing framework. It discusses dispersive methods, synergistic dispersion, and in-situ growth, which have yielded smart 3D-printed structures with unique functionality for specific applications. This review also focuses on nanomaterial alignment in 3D printing, detailing methods that enhance selective deposition and orientation of nanofillers within established and customized printing techniques. By emphasizing alignment strategies, we explore their impact on the performance of 3D-printed composites and highlight potential applications that benefit from ordered nanoparticles. Through these continuing efforts, this review shows that the design and development of the new class of nanomaterials are crucial to developing the next generation of smart 3D printed architectures with versatile abilities for advanced structures with exceptional performance.

Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on "bio-orthogonal chemistry", combining hyaluronic acid and polyethylene glycol (PEG) matrices co-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.

PAI-1 siRNA-loaded biomimetic nanoparticles for ameliorating diminished ovarian reserve and inhibiting ovarian fibrosis.

With specific and inherent mRNA cleaving activity, small interfering RNA against pro-fibrosis factor (PAI-1 siRNA, siPAI-1) has demonstrated the fucntion for preventing diminished ovarian reserve (DOR). Moreover, safe nanomaterials have provided ideal tools for delivering siRNA to the targeted cells to obtain high therapeutic efficacy. In order to improve the preventing capability of siPAI-1 for DOR , we synthesized one kind of biomimetic Poly (lactic-co-glycolic acid) copolymer (PLGA)-based nanoparticles (siPAI-1@PLGA@M-FSHL, abbreviated as SPMF). siPAI-1 was assembled into cationic PLGA nanoparticles, following with macrophage membrane coating (M) and FSHL81-95 peptide modification. SPMF NPs significantly enhanced cellular uptake and gene silencing efficiency in KGN cells in vitro. In vivo assay demonstrated that SPMF NPs can targetedly accumulate in the ovarian of DOR mice with Cyclophosphamide treatment (80 mg/kg/week, 2 weeks) and remarkably downregulate the levels of PAI-1 in ovarian, which finally resulted in the effective suppression of ovary fibrosis and improved the chemotherapy-induced follicle loss to increase the number of primordial, secondary, antral follicles by 62.05 %, 54.92 % and 64.37 %, respectively, compared with DOR group. In summary, this study demonstrates that siPAI-1-loaded SPMF with high safety and efficacy can potentially alleviate DOR by inhibiting the overexpression of PAI-1 in the ovarian.