Nanoparticle System Research Articles

Susceptibility in a Coupled Double Quantum Dot-Metal Nanoparticle System under Standing Wave Field

Susceptibility in a Coupled Double Quantum Dot-Metal Nanoparticle System under Standing Wave Field

Noninvasive platelet membrane-coated Fe3O4 nanoparticles identify vulnerable atherosclerotic plaques.

Vulnerable atherosclerotic plaques serve as the primary pathological basis for fatal cardiovascular and cerebrovascular diseases. The precise identification and treatment of these vulnerable plaques hold paramount clinical importance in mitigating the incidence of myocardial infarction and stroke. Nevertheless, the identification of vulnerable plaques within the diffuse atherosclerotic plaques dispersed throughout the systemic circulation continues to pose a substantial challenge in clinical practice. Double emulsion solvent evaporation method, specifically the water-in-oil-in-water (W/O/W) technique, was employed to fabricate Fe3O4-based poly (lactic-co-glycolic acid) (PLGA) nanoparticles (Fe3O4@PLGA). Platelet membranes (PM) were extracted through hypotonic lysis, followed by ultrasound-assisted encapsulation onto the surface of Fe3O4@PLGA, resulting in the formation of PM-coated Fe3O4 nanoparticles (PM/Fe3O4@PLGA). Characterization of PM/Fe3O4@PLGA involved the use of dynamic light scattering, transmission electron microscopy, western blotting, and magnetic resonance imaging (MRI). A model of atherosclerotic vulnerable plaques was constructed by carotid artery coarctation and a high-fat diet fed to ApoE-/- (Apolipoprotein E knockout) mice. Immunofluorescence and MRI techniques were employed to verify the functionality of PM/Fe3O4@PLGA. In this study, we initially synthesized Fe3O4@PLGA as the core material. Subsequently, a platelet membrane was employed as a coating for the Fe3O4@PLGA, aiming to enable the detection of vulnerable atherosclerotic plaques through MRI. In vitro, PM/Fe3O4@PLGA not only exhibited excellent biosafety but also showed targeted collagen characteristics and MR imaging performance. In vivo, the adhesion of PM/Fe3O4@PLGA to atherosclerotic lesions was confirmed in a mouse model of vulnerable atherosclerotic plaques. Simultaneously, PM/Fe3O4@PLGA as a novel contrast agent for MRI has shown effective identification of vulnerable atherosclerotic plaques. In terms of safety profile in vivo, PM/Fe3O4@PLGA has not demonstrated significant organ toxicity or inflammatory response in the bloodstream. In this study, we successfully developed a platelet-membrane-coated nanoparticle system for the targeted delivery of Fe3O4@PLGA to vulnerable atherosclerotic plaques. This innovative system allows for the visualization of vulnerable plaques using MRI, thereby demonstrating its potential for enhancing the clinical diagnosis of vulnerable atherosclerotic plaques.

Developing MiR-133a Zipper Nanoparticles for Targeted Enhancement of Thermogenic Adipocyte Generation.

Existing delivery methods for RNAi therapeutics encounter challenges, including stability, specificity, and off-target effects, which restrict their clinical effectiveness. In this study, a novel miR-133a zipper nanoparticle (NP) system that integrates miRNA zipper technology with rolling circle transcription (RCT) to achieve targeted delivery and specific regulation of miR-133a in adipocytes, is presented. This innovative approach can greatly enhance the delivery and release of miR-133a zippers, increasing the expression of thermogenic genes and mitochondrial biogenesis. he miR-133a zipper NP is utilized for the delivery of miRNA zipper-blocking miR-133a, an endogenous inhibitor of Prdm16 expression, to enhance the thermogenic activity of adipocytes by modulating their transcriptional program. Inhibition of miR-133a through the miR-133a zipper NP leads to more significant upregulation of thermogenic gene expression (Prdm16 and Ucp1) than with the free miR-133a zipper strand. Furthermore, miR-133a zipper NPs increase the number of mitochondria and induce heat production, reducing the size of 3D adipose spheroids. In short, this study emphasizes the role of RNA NPs in improving RNAi stability and specificity and paves the way for broader applications in gene therapy. Moreover, this research represents a significant advancement in RNAi-based treatments, pointing toward a promising direction for future therapeutic strategies.

Implications of size dispersion on X-ray scattering of crystalline nanoparticles: CeO2 as a case study

Controlling the shape and size dispersivity and crystallinity of nanoparticles (NPs) has been a challenge in identifying these parameters' role in the physical and chemical properties of NPs. The need for reliable quantitative tools for analyzing the dispersivity and crystallinity of NPs is a considerable problem in optimizing scalable synthesis routes capable of controlling NP properties. The most common tools are electron microscopy (EM) and X-ray scattering techniques. However, each technique has different susceptibility to these parameters, implying that more than one technique is necessary to characterize NP systems with maximum reliability. Wide-angle X-ray scattering (WAXS) is mandatory to access information on crystallinity. In contrast, EM or small-angle X-ray scattering (SAXS) is required to access information on whole NP sizes. EM provides average values on relatively small ensembles in contrast to the bulk values accessed by X-ray techniques. Besides the fact that the SAXS and WAXS techniques have different susceptibilities to size distributions, SAXS is easily affected by NP–NP interaction distances. Because of all the variables involved, there have yet to be proposed methodologies for cross-analyzing data from two techniques that can provide reliable quantitative results of dispersivity and crystallinity. In this work, a SAXS/WAXS-based methodology is proposed for simultaneously quantifying size distribution and degree of crystallinity of NPs. The most reliable easy-to-access size result for each technique is demonstrated by computer simulation. Strategies on how to compare these results and how to identify NP–NP interaction effects underneath the SAXS intensity curve are presented. Experimental results are shown for cubic-like CeO2 NPs. WAXS size results from two analytical procedures are compared, line-profile fitting of individual diffraction peaks in opposition to whole pattern fitting. The impact of shape dispersivity is also evaluated. Extension of the proposed methodology for cross-analyzing EM and WAXS data is possible.

Thermal conductivity of irregularly shaped nanoparticles from equilibrium molecular dynamics

The computation of thermal conductivity for finite nanoparticulate systems, particularly those of irregular shapes, poses significant challenges. The nonequilibrium molecular dynamics (NEMD) methods has been extensively utilized in numerous prior studies for the computation of thermal conductivity of nanoparticles. One of our recent works (Dong et al 2021 Phys. Rev. B 103 035417) proposed that equilibrium molecular dynamics (EMD) methods can be used for the simulation of thermal conductivity of finite-scale systems and demonstrated their equivalence to NEMD methods. In this study, we investigated the application of the (EMD) approach for the computation of thermal conductivity in zero-dimensional nanoparticles. In our initial step, we merged both methodologies to substantiate the equivalence in thermal conductivity calculation for cube and cylinder nanoparticles. After filtering the data, we confirmed the usefulness of EMD for evaluating the thermal conductivity of zero-dimensional materials. The NEMD method faces challenges in accurately predicting thermal conductivity in nanoparticle systems with a varying cross-sectional area along the transport direction, whereas EMD methods can be utilized to estimate thermal conductivity when the volume is known. In a subsequent study, we used the state-of-the-art machine learning potential to calculate the thermal conductivity of spherical nanoparticles and compared the results with those obtained using the classical Tersoff potential. Ultimately, we predicted the thermal conductivity of nanoparticles with various geometries in all directions. Our findings collectively demonstrate the simplicity and effectiveness of employing EMD methods for calculating thermal conductivity in nanoparticle systems, thereby opening up new avenues for investigating thermal transport properties in particle systems as well as nanopders.

Convergence and accuracy of FDTD modelling for periodic plasmonic systems

Despite the widespread use of the finite-difference time-domain (FDTD) method for modeling plasmonic systems, there is a lack of detailed convergence and accuracy studies for periodic nanoparticle systems in which both particle radius and interparticle distance are critical parameters. Using an in-house parallelized 3D-FDTD code for which we implemented interface field averaging, convergence and accuracy were evaluated for various spherical particle radii, inter-distances, and radius-to-mesh size ratios. We found that Interface Field Averaging (IFA) FDTD improved accuracy and convergence with respect to per-component (Per-C) meshing. In the worst case of this study, the convergence error decreased from 4.9% to 2.6% only by using IFA. Accuracy was verified by benchmarking our simulation results with COMSOL Multiphysics software. Furthermore, we notice that there exists no general rule for choosing the mesh size. Careful convergence testing should therefore be carried out systematically.

The Catalytic Activity of Magnetic Surfaces

High-performance catalysts for the oxygen reduction and hydrogen evolution reactions (ORR and HER, respectively) are highly sought-after, particularly with the commitment of numerous agencies to the removal of conventional gas vehicles in the next few decades. Surprisingly little focus has been placed on the development of magnetic models to describe these systems. The current work will review the current understanding of surface heterogeneous catalysis across select magnetic surfaces, with attention focused on studies involving extended surfaces, which inherently are more accessible to fundamental analysis than the more applied nanoparticle systems. However, even the most up-to-date magnetic variants of this theory have focused on the tight binding limit of the d-band model. In this limit, the reactivity of the surface is governed by the position of the center of the d-band, and the model does not account for the higher moments of the d-band, such as the width, asymmetry, and modality. A summary of the theory supporting this analysis will be presented, along with a summary of the current literature on this level of analysis. The review will then conclude with a discussion of suggested directions for future investigations.

A Review on Herbal Drug Nanotechnology and Nanomedicine

The review's goal is to talk about both nanomedicine and herbal medicine nanotechnology. Since ancient times, herbal remedies have been widely utilised and acknowledged by medical professionals and patients for their potent positive benefits and reduced risk of side effects when compared to conventional treatment. Here, we provide an overview of nanomedicine, discuss the use of nanoparticles in herbal medicine, discuss the obstacles facing nanotechnology, and discuss several formulations of herbal nanomedicine. In order to improve patient compliance and reduce the need for repeated dosages, the evaluation concentrated on a novel strategy that tackles the drawbacks of the conventional drug delivery method. It also highlights current advancements in nanomedicine that have been impacted by nanotechnology, such as nanoparticulate systems. Additionally, this assessment notes that the drug's efficacy and bioavailability have improved. By creating novel medicine formulations with herbal ingredients, it will be achievable. NDDS is an effective medication that minimises negative effects and improves bioavailability, in addition to lowering dose frequency. Nanotechnology is a revolutionary medicine delivery system. Furthermore, the study demonstrates that nano-sized constituents for herbal medications may be used in the future to improve pharmacological activity while lowering dosage requirements and adverse effects. Research indicates that NDDS may have a significant role in the fight against a variety of chronic illnesses, such as diabetes, cancer, and asthma. Reviewing new drug delivery methods and Herbal remedies are the goal of these. Products made from herbs and used for medical purposes are referred to as phytomedicinal products. It includes one or more active ingredients derived from herbs. The researcher in the recent creation of herbal drug nanomedicine receives help and guidance from this review.

Exploring the Formulation and Approaches of Injectable Hydrogels Utilizing Hyaluronic Acid in Biomedical Uses.

The characteristics of injectable hydrogels make them a prime contender for various biomedical applications. Hyaluronic acid is an essential component of the matrix surrounding the cells; moreover, hyaluronic acid's structural and biochemical characteristics entice researchers to develop injectable hydrogels for various applications. However, due to its poor mechanical properties, several strategies are used to produce injectable hyaluronic acid hydrogel. This review summarizes published studies on the production of injectable hydrogels based on hyaluronic acid polysaccharide polymers and the biomedical field's applications for these hydrogel systems. Hyaluronic acid-based hydrogels are divided into two categories based on their injectability mechanisms: in situ-forming injectable hydrogels and shear-thinning injectable hydrogels. Many crosslinking methods are used to create injectable hydrogels; chemical crosslinking techniques are the most frequently investigated technique. Hybrid injectable hydrogel systems are widely investigated by blending hyaluronic acid with other polymers or nanoparticulate systems. Injectable hyaluronic acid hydrogels were thoroughly investigated and proven to demonstrate potential in various medical fields, including delivering drugs and cells, tissue repair, and wound dressings.

Virus-like structures for combination antigen protein mRNA vaccination

Improved vaccination requires better delivery of antigens and activation of the natural immune response. Here we report a lipid nanoparticle system with the capacity to carry antigens, including mRNA and proteins, which is formed into a virus-like structure by surface decoration with spike proteins, demonstrating application against SARS-CoV-2 variants. The strategy uses S1 protein from Omicron BA.1 on the surface to deliver mRNA of S1 protein from XBB.1. The virus-like particle enables specific augmentation of mRNAs expressed in human respiratory epithelial cells and macrophages via the interaction the surface S1 protein with ACE2 or DC-SIGN receptors. Activation of macrophages and dendritic cells is demonstrated by the same receptor binding. The combination of protein and mRNA increases the antibody response in BALB/c mice compared with mRNA and protein vaccines alone. Our exploration of the mechanism of this robust immunity suggests it might involve cross-presentation to diverse subsets of dendritic cells ranging from activated innate immune signals to adaptive immune signals.

Chitosan-modified manganese oxide-conjugated methotrexate nanoparticles delivering 5-aminolevulinic acid as a dual-modal T1-T2* MRI contrast agent in U87MG cell detection.

Glioblastoma multiforme is a highly aggressive form of brain cancer, and early diagnosis plays a pivotal role in improving patient survival rates. In this regard, molecular magnetic resonance imaging has emerged as a promising imaging modality due to its exceptional sensitivity to minute tissue changes and the ability to penetrate deep into the brain. This study aimed to assess the efficacy of a novel contrast agent in detecting gliomas during MRI scans. The contrast agent utilized modified chitosan coating on manganese oxide nanoparticles. The modification included adding methotrexate and 5-aminolevulinic acid (MnO2/CS@5-ALA-MTX) to target cells with overexpressed folate receptors and breaking down excess hydrogen peroxide in tumor tissue, resulting in enhanced signal intensity in T1-weighted MR images but diminished signal intensity in T2*-weighted MR images. The nanosystem was characterized and evaluated in MR imaging, safety, and ability to target cells both in vivo and in vitro. MTX-free nanoparticles (MnO2/CS@5-ALA NPs) had no obvious cytotoxicity on cell lines U87MG and NIH3T3 after 24/48 h at a concentration of up to 160 µgr/mL (cell viability more than 80%). In this system, methotrexate enables tumor targeting and the MnO2/5-ALA improves T1-T2*-weighted MRI. In addition, MRI scans of mice with M109 carcinoma indicated significant tumor uptake and NP capacity to improve the positive contrast effect. This developed MnO2/CS@5-ALA-MTX nanoparticle system may exhibit great potential in the accurate diagnosis of folate receptor over-expressing cancers such as glioblastoma.

Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer’s disease

Brain-targeted gene delivery across the blood-brain barrier (BBB) is a significant challenge in the 21st century for the healthcare sector, particularly in developing an effective treatment strategy against Alzheimer’s disease (AD). The Internal architecture of the brain capillary endothelium restricts bio-actives entry into the brain. Additionally, therapy with nucleic acids faces challenges like vulnerability to degradation by nucleases and potential immune responses. Functionalized nanocarrier-based gene delivery approaches have resulted in safe and effective platforms. These nanoparticles (NPs) have demonstrated efficacy in protecting nucleic acids from degradation, enhancing transport across the BBB, increasing bioavailability, prolonging circulation time, and regulating gene expression of key proteins involved in AD pathology. We provided a detailed review of several nanocarriers and targeting ligands such as cell-penetrating peptides (CPPs), endogenous proteins, and antibodies. The utilization of functionalized NPs extends beyond a singular system, serving as a versatile platform for customization in related neurodegenerative diseases. Only a few numbers of bioactive regimens can go through the BBB. Thus, exploring functionalized NPs for brain-targeted gene delivery is of utmost necessity. Currently, genes are considered high therapeutic potential molecules for altering any disease-causing gene. Through surface modification, nanoparticulate systems can be tailored to address various diseases by replacing the target-specific molecule on their surface. This review article presents several nanoparticulate delivery systems, such as lipid NPs, polymeric micelles, exosomes, and polymeric NPs, for nucleic acids delivery to the brain and the functionalization strategies explored in AD research.

Drug Delivery Systems of Betulin and Its Derivatives: An Overview.

Natural origin products are regarded as promising for the development of new therapeutic therapies with improved effectiveness, biocompatibility, reduced side effects, and low cost of production. Betulin (BE) is very promising due to its wide range of pharmacological activities, including its anticancer, antioxidant, and antimicrobial properties. However, despite advancements in the use of triterpenes for clinical purposes, there are still some obstacles that hinder their full potential, such as their hydrophobicity, low solubility, and poor bioavailability. To address these concerns, new BE derivatives have been synthesized. Moreover, drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. The aim of this manuscript is to summarize the recent achievements in the field of delivery systems of BE and its derivatives. This review also presents the BE derivatives mostly considered for medical applications. The electronic databases of scientific publications were searched for the most interesting achievements in the last ten years. Thus far, it is mostly nanoparticles (NPs) that have been considered for the delivery of betulin and its derivatives, including organic NPs (e.g., micelles, conjugates, liposomes, cyclodextrins, protein NPs), inorganic NPs (carbon nanotubes, gold NPs, silver), and complex/hybrid and miscellaneous nanoparticulate systems. However, there are also examples of microparticles, gel-based systems, suspensions, emulsions, and scaffolds, which seem promising for the delivery of BE and its derivatives.

The HCoV-HKU1 N-terminal domain binds a wide range of 9-O-acetylated sialic acids presented on different glycan cores.

Coronaviruses recognize a wide array of protein and glycan receptors using the S1 subunit of the spike (S) glycoprotein. The S1 subunit contains two functional domains: the N-terminal (S1-NTD) and C-terminal (S1-CTD). The S1-NTD of SARS-CoV-2, MERS-CoV, and HCoV-HKU1 possess an evolutionarily conserved glycan binding cleft that facilitates weak interactions with sialic acids on cell surfaces. HCoV-HKU1 employs 9-O-acetylated α2-8-linked disialylated structures for initial binding, followed by TMPRSS2 receptor binding and virus-cell fusion. Here, we demonstrate that HCoV-HKU1 NTD has a broader receptor binding repertoire than previously recognized. We presented HCoV-HKU1 NTD Fc chimeras on a nanoparticle system to mimic the densely decorated surface of HCoV-HKU1. These proteins were expressed by HEK293S GNTI- cells, generating species carrying Man-5 structures, often observed near the receptor binding site of CoVs. This multivalent presentation of high-mannose-containing NTD proteins revealed a much broader receptor binding profile compared to its fully glycosylated counterpart. Using glycan microarrays, we observed that 9-O-acetylated α2-3 linked sialylated LacNAc structures are also bound, comparable to OC43 NTD, suggesting an evolutionarily conserved glycan-binding modality. Further characterization of receptor specificity indicated promiscuous binding towards 9-O-acetylated sialoglycans, independent of the glycan core (glycolipids, N- or O-glycans). We demonstrate that HCoV-HKU1 may employ additional sialoglycan receptors to trigger conformational changes in the spike glycoprotein to expose the S1-CTD for proteinaceous receptor binding.

Ameliorative delivery of docetaxel and curcumin using PEG decorated lipomers: A cutting-edge in-vitro/ in-vivo appraisal

The development of a PEG-decorated lipid-polymer hybrid system camouflaged with natural and synthetic chemotherapeutic moieties is an influential approach melding the biomimetic properties of long-circulating vesicles to utilize different mechanisms to dwindle the tumor growth. Therefore, a safe and efficient lipid-coated nano-particulate system (LCNPs) was proposed to investigate the in-vitro, ex-vivo and in-vivo demeanors of such amalgamation.Docetaxel loaded PLGA nanoparticles (DTX-NPs) were prepared by solvent evaporation while curcumin liposomes were mapped out using the film hydration method. Physicochemical characterizations were executed in terms of size, surface morphology, differential scanning calorimetry (DSC) and fourier-transform infrared spectroscopy (FTIR). In-vitro cytotoxicity was effectuated using MCF-7 cell line. Hemolysis, erythrocyte aggregation and acute in-vivo toxicity were carried out to establish the biocompatibility. The hydrodynamic diameters of samples were in the nano-range and corresponded to the findings of scanning electron microscopy (SEM) and atomic force microscopy (AFM). The absence of distinctive peaks of DTX-NPs in FTIR and DSC analysis of LCNPs depicts the shielding of the lipid bilayer over the nanoparticle. Cytotoxicity induced by the LCNPs represented the efficient delivery of cargo to the tumor cells. LCNPs also exhibited the least toxicity under ex-vivo and in-vivo circumstances compared to free drugs. Additionally, histological studies showed no evidence of substantial necrosis. Additionally, histological studies showed no evidence of notable necrosis.

Baicalin-loaded Polydopamine modified ZIF-8 NPs inhibits myocardial ischemia/reperfusion injury in rats

Baicalin (BAN) has shown promise in alleviating myocardial ischemia/reperfusion (I/R) injury, yet its limited solubility and biocompatibility have hindered its application. Developing drug delivery systems is a promising strategy to enhance the therapeutic potential of BAN in the context of I/R injury. This study aims to prepare a BAN-loaded nanodrug system using polydopamine (PDA)-modified Zeolitic imidazolate framework-8 (ZIF-8) as a carrier, with the goal of improving BAN's mitigating effects on I/R injury. We prepared the BAN nanoparticles (NPs) system, PZB NPs, using ZIF-8 as the carrier. The system was characterized in terms of morphology, particle size, zeta potential, and X-ray diffraction (XRD). We assessed the cytotoxicity of PZB NPs in H9c2 cells, investigated its effects and mechanisms in H/R-induced H9c2 cells, and evaluated its ability to alleviate myocardial I/R injury in rats. PZB NPs exhibited good dispersion, with a BAN loading efficiency of 26.43 ± 1.55%, a hydrated particle size of 102.21 ± 1.19 nm, and a zeta potential of −24.84 ± 0.07 mV. It displayed slow and sustained drug release in an acidic environment (pH 5.5). In vitro studies revealed that PZB NPs was non-cytotoxic and significantly enhanced the recovery of H/R injury H9c2 cell viability. PZB NPs suppressed cell apoptosis, activated the Nrf2/HO-1 pathway, and cleared ROS. In vivo study demonstrated that PZB NPs significantly reduced infarct size, ameliorated fibrosis and improved heart function. The PZB NPs markedly enhances BAN's ability to alleviate I/R injury, both in vitro and in vivo, offering a promising drug delivery system for clinical applications.

Folate Receptor Targeting Mn(II) Complex Encapsulated Porous Silica Nanoparticle as an MRI Contrast Agent for Early-State Detection of Cancer.

Cancer is recognized as one of the major causes of mortality, however, early-stage detection can increase the survival chance greatly. It is recognized that folate receptors are gradually overexpressed in the cellular membrane with the progress of cancer from stage 1 to stage 4. Utilizing the fact, herein, developed a porous silica nanoparticle system C1@SiO2-FA-NP; A) impregnated with thermodynamically stable Mn(II) complex (1) molecules within the core of the nanoparticle, and B) surface functionalized with folate units. It exhibited a high longitudinal relaxivity value r1 = 21.45 mM-1s-1 that substantially increased to r1 = 40.97 mM-1s-1 in the presence of 0.67mM concentration of BSA under the physiological condition. The in vitro fluorescent images after surface conjugation of C1@SiO2-FA-NP with FITC (fluorescein isothiocyanate) buttressed the inclusion of the nanoparticle exclusively within the cancerous HeLa cells than that of healthy HEK293 cells. The importance of the surface-bound folate unit in the nanoparticle is further established by comparing the fluorescent images of HeLa cells in the absence of the group. Finally, the applicability of C1@SiO2-FA-NP as the T1-weighted MRI contrast agent for early-stage cancer diagnosis is established within C57BL/6 mice after infecting the mice with HeLa cells.

Matrix Metalloproteinase- and pH-Sensitive Nanoparticle System Enhances Drug Retention and Penetration in Glioblastoma.

Glioblastoma (GBM) is a primary malignant brain tumor with limited therapeutic options. One promising approach is local drug delivery, but the efficacy is hindered by limited diffusion and retention. To address this, we synthesized and developed a dual-sensitive nanoparticle (Dual-NP) system, formed between a dendrimer and dextran NPs, bound by a dual-sensitive [matrix metalloproteinase (MMP) and pH] linker designed to disassemble rapidly in the tumor microenvironment. The disassembly prompts the in situ formation of nanogels via a Schiff base reaction, prolonging Dual-NP retention and releasing small doxorubicin (Dox)-conjugated dendrimer NPs over time. The Dual-NPs were able to penetrate deep into 3D spheroid models and detected at the tumor site up to 6 days after a single intratumoral injection in an orthotopic mouse model of GBM. The prolonged presence of Dual-NPs in the tumor tissue resulted in a significant delay in tumor growth and an overall increase in survival compared to untreated or Dox-conjugated dendrimer NPs alone. This Dual-NP system has the potential to deliver a range of therapeutics for efficiently treating GBM and other solid tumors.

Nanoparticles-encapsulated doxorubicin alleviates drug resistance of osteosarcoma via inducing ferroptosis

To determine the effects of polymeric nanoparticle for doxorubicin (Dox) delivery and treatment of drug-resistant Osteosarcoma (OS) cells. Methoxy-polyethylene glycol amino (mPEG-NH2) and platinum bio-mimetic polycaprolactone-cysteine (PtBMLC) were crosslinked to obtain glutathione (GSH)-responsive mPEG-NH2-PtBMLC polymer to encapsulate Dox (named as Nano-Dox). The particle size and zeta potential of the nanoparticles were measured, and internalization of Dox by OS cells was observed. After treatment with Nano-Dox, cell proliferation was determined by cell counting kit 8 (CCK-8) and colony formation assay. Cell migration and invasion were determined by Transwell assay. Cell cycle arrest was assessed by flow cytometry. The induction of ferroptosis was analyzed by abnormal accumulation of total iron, Fe2+. Nano-Dox exhibited a stronger localization in OS cells (p < 0.01). Nano-Dox induced more significant suppression of drug-resistant OS cell growth (p < 0.01), migration (p < 0.01), and invasion (p < 0.01), compared with the single Dox treatment group, along with decreased expression of N-cadherin, Snail, and Vimentin, suggesting impaired cancer migration and invasion. The treatment with Nano-Dox induced notable cell cycle arrest at G0/G1 phase (p < 0.01) and accumulation of iron, Fe2+, and MDA (p < 0.01), as well as suppressed the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11. Administration of ferroptosis inhibitor (Fer-1) reversed the anti-proliferation effects of Nano-Dox (p < 0.01). The Dox delivered by the polymeric nanoparticle system notably enhanced its effects on suppressing the growth, migration, and invasion of drug-resistant OS cells via inducing ferroptosis. The application of environment response polymer enhanced the delivery of Dox and the therapeutic effects on OS.

Evaluation of the biodistribution and preliminary safety profile of a novel brain-targeted manganese dioxide-based nanotheranostic system for Alzheimer’s disease

A novel brain-targeted and reactive oxygen species-activatable manganese dioxide containing nanoparticle system functionalized with anti-amyloid-β antibody (named aAβ-BTRA-NC) developed by our group has shown great promise as a highly selective magnetic resonance imaging (MRI) contrast agent for early detection and multitargeted disease-modifying treatment of Alzheimer’s disease (AD). To further evaluate the suitability of the formulation for future clinical application, we investigated the safety, biodistribution, and pharmacokinetic profile of aAβ-BTRA-NC in a transgenic TgCRND8 mouse AD model, wild type (WT) littermate, and CD-1 mice. Dose-ascending studies demonstrated that aAβ-BTRA-NC was well-tolerated by the animals up to 300 μmol Mn/kg body weight [b.w.], 3 times the efficacious dose for early AD detection without apparent adverse effects; Histopathological, hematological, and biochemical analyses indicated that a single dose of aAβ-BTRA-NC did not cause any toxicity in major organs. Immunotoxicity data showed that aAβ-BTRA-NC was safer than commercially available gadolinium-based MRI contrast agents at an equivalent dose of 100 μmol/kg b.w. of metal ions. Intravenously administered aAβ-BTRA-NC was taken up by main organs with the order of liver, kidneys, intestines, spleen, followed by other organs, and cleared after one day to one week post injection. Pharmacokinetic analysis indicated that the plasma concentration profile of aAβ-BTRA-NC followed a 2-compartmental model with faster clearance in the AD mice than in the WT mice. The results suggest that aAβ-BTRA-NC exhibits a strong safety profile as a nanotheranostic agent which warrants more robust preclinical development for future clinical applications.