International Journal of Nanomedicine最新文献

Introduction: The therapeutic efficacy for airway allergies needs to be improved. Th2 polarization is a primary pathological feature of airway allergies. We constructed chimeric antigen-LgDNA (Lactobacillus rhamnosus DNA) nanoparticles (CAP-NPs). The effects of CAP-NPs on reconciling airway Th2 polarization were tested.

Methods: In this study, disulfide bond-linked antigen-major histocompatibility complex II (MHC II)-LgDNA nanoparticles (NPs) were constructed and designated CAP-NPs. An airway Th2 polarization mouse model was established to test the effects of CAP-NPs on suppressing the Th2 response.

Results: The CAP-NP components of ovalbumin (OVA), major histocompatibility complex II (MHC II), and LgDNA were confirmed in a series of laboratory tests. The CAP-NPs remained stable at pH7.2 for at least 96 h. In in vitro experiments, CAP-NPs bound to the surface of OVA-specific CD4⁺ T cells, which resulted in apoptosis of the antigen-specific CD4⁺ T cells. Removal of any of the three components from the NPs abolished the induction of apoptosis of antigen specific CD4⁺ T cells. CAP-NPs increased the expression of lysine-specific demethylase 5A (KDM5A) in CD4⁺ T cells. Histone H3K9 and the gene promoter of caspase 8 were demethylated by KDM5A, which led to transcription and expression of the caspase 8 gene. Administration of CAP-NPs significantly alleviated experimental airway Th2 polarization through activating the caspase 8-apoptosis signaling pathway.

Discussion: In this paper, we constructed CAP-NPs that could induce antigen-specific CD4⁺ T cell apoptosis. Administration of CAP-NPs efficiently alleviated experimental airway Th2 polarization.

Introduction: Alzheimer's disease (AD), a neurodegenerative condition, stands as the most prevalent form of dementia. Its complex pathological mechanisms and the formidable blood-brain barrier (BBB) pose significant challenges to current treatment approaches. Oxidative stress is recognized as a central factor in AD, underscoring the importance of antioxidative strategies in its treatment. In this study, we developed a novel brain-targeted nanoparticle, Ce/Zr-MOF@Cur-Lf, for AD therapy.

Methods: Layer-by-layer self-assembly technology was used to prepare Ce/Zr-MOF@Cur-Lf. In addition, the effect on the intracellular reactive oxygen species level, the uptake effect by PC12 and bEnd.3 cells and the in vitro BBB permeation effect were investigated. Finally, the mouse AD model was established by intrahippocampal injection of Aβ_1-42, and the in vivo biodistribution, AD therapeutic effect and biosafety of the nanoparticles were researched at the animal level.

Results: As anticipated, Ce/Zr-MOF@Cur-Lf demonstrated efficient BBB penetration and uptake by PC12 cells, leading to attenuation of H₂O₂-induced oxidative damage. Moreover, intravenous administration of Ce/Zr-MOF@Cur-Lf resulted in rapid brain access and improvement of various pathological features of AD, including neuronal damage, amyloid-β deposition, dysregulated central cholinergic system, oxidative stress, and neuroinflammation.

Conclusion: Overall, Ce/Zr-MOF@Cur-Lf represents a promising approach for precise brain targeting and multi-target mechanisms in AD therapy, potentially serving as a viable option for future clinical treatment.

With the in-depth knowledge of the pathological and physiological characteristics of the intestinal barrier-portal vein/intestinal lymphatic vessels-systemic circulation axis, oral targeted drug delivery is frequently being renewed. With many advantages, such as high safety, convenient administration, and good patient compliance, many researchers have begun to explore targeted drug delivery from intravenous injections to oral administration. Over the past few decades, the fields of materials science and nanomedicine have produced various drug delivery platforms that hold great potential in overcoming the multiple barriers associated with oral drug delivery. However, the oral transport of particles into the systemic circulation is extremely difficult due to immune rejection and biochemical invasion in the intestine, which limits absorption and entry into the bloodstream. The feasibility of the oral delivery of targeted drugs to sites outside the gastrointestinal tract (GIT) is unknown. This article reviews the biological barriers to drug absorption, the in vivo fate and transport mechanisms of drug carriers, the theoretical basis for oral administration, and the impact of carrier structural evolution on oral administration to achieve this goal. Finally, this article reviews the characteristics of different nano-delivery systems that can enhance the bioavailability of oral therapeutics and highlights their applications in the efficient creation of oral anticancer nanomedicines.

The endocrine system regulates many biological systems, and disruptions may result in disorders, such as diabetes, thyroid dysfunction, Cushing's syndrome, and obesity. The total incidence of endocrine illnesses was found to be 47.4%, excluding type 2 diabetes mellitus, with a significant frequency of newly diagnosed endocrine disorders. Nanotechnology manipulates particles at the atomic and molecular levels, opening up new paths for studying disease etiology and therapeutic alternatives. The goal of using nanomaterials in the treatment of endocrine illnesses is to create endogenous nano-biosensors that can detect even modest changes in hormone levels and react spontaneously to restore normal function. The size and surface characteristics of nanoparticles enhances the sensitivity in nano-sensors and are functionalized for targeted drug delivery. Nano-sized carriers composed of lipids, polymers, carbon, or metals have been shown to work much better than standard drug delivery methods. Nanoparticles (NPs) offer various advantages over current methods for diagnosing and treating endocrine disorders, acting as hydrogels for insulin delivery and wound healing. Incorporating selenium NPs into inorganic nanoparticles enhances their bioactivity and targeted delivery. Gold NPs show a promising precise insulin delivery. Mesoporous silica NPs maintain glycemic level effectively and lipid and polymeric NPs protect drugs from degradation in the gastrointestinal tract. Carbon nanotubes (CNTs) have become popular in thyroid surgeries. These characteristics make nanoparticles valuable for developing effective diagnostic and therapeutic systems. NP-based medicines have been thoroughly researched in order to identify the beginning point for the creation of theranostics, which may function in two ways: as imaging agents or therapeutics. The study posits that nanotechnology bridges diagnostics and therapies, potentially revolutionizing endocrine disorder treatments. This review delves into nanotechnology techniques, emphasizing their applications in diagnosing and treating diabetes mellitus.

Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.

Purpose: Renal cell carcinoma (RCC) is the most common and lethal type of urogenital cancer, with one-third of new cases presenting as metastatic RCC (mRCC), which, being the seventh most common cancer in men and the ninth in women, poses a significant challenge. For patients with poor prognosis, temsirolimus (TEM) has been approved for first-line therapy, possessing pharmacodynamic activities that block cancer cell growth and inhibit proliferation-associated proteins. However, TEM suffers from poor water solubility, low bioavailability, and systemic side effects. This study aims to develop a novel drug formulation for the treatment of RCC.

Methods: In this study, amphiphilic block copolymer (poly(ethylene glycol) monomethyl ether-poly(beta-amino ester)) (mPEG-PBAE) was utilized as a drug delivery vehicle and TEM-loaded micelles were prepared by thin-film hydration method by loading TEM inside the nanoparticles. Then, the molecular weight of mPEG-PBAE was controlled to make it realize hydrophobic-hydrophilic transition in the corresponding pH range thereby constructing pH-responsive TEM-loaded micelles. Characterization of pH-responsive TEM-loaded nanomicelles particle size, potential and micromorphology while its determination of drug-loading properties, in vitro release properties. Finally, pharmacodynamics and hepatorenal toxicity were further evaluated.

Results: TEM loading in mPEG-PBAE increased the solubility of TEM in water from 2.6 μg/mL to more than 5 mg/mL. The pH-responsive TEM-loaded nanomicelles were in the form of spheres or spheroidal shapes with an average particle size of 43.83 nm and a Zeta potential of 1.79 mV. The entrapment efficiency (EE) of pH-responsive TEM nanomicelles with 12.5% drug loading reached 95.27%. Under the environment of pH 6.7, the TEM was released rapidly within 12 h, and the release rate could reach 73.12% with significant pH-dependent characteristics. In vitro experiments showed that mPEG-PBAE preparation of TEM-loaded micelles had non-hemolytic properties and had significant inhibitory effects on cancer cells. In vivo experiments demonstrated that pH-responsive TEM-loaded micelles had excellent antitumor effects with significantly reduced liver and kidney toxicity.

Conclusion: In conclusion, we successfully prepared pH-responsive TEM-loaded micelles. The results showed that pH-responsive TEM-loaded micelles can achieve passive tumor targeting of TEM, and take advantage of the acidic conditions in tumor tissues to achieve rapid drug release.

Fullerenes hold tremendous potential as alternatives to conventional chemotherapy or radiotherapy for tumor treatment due to their abilities to photodynamically kill tumor cells, destroy the tumor vasculature, inhibit tumor metastasis and activate anti-tumor immune responses, while protecting normal tissue through antioxidative effects. The symmetrical hollow molecular structures of fullerenes with abundant C=C bonds allow versatile chemical modification with diverse functional groups, metal clusters and biomacromolecules to synthesize a wide range of fullerene derivatives with increased water solubility, improved biocompatibility, enhanced photodynamic properties and stronger targeting abilities. This review introduces the anti-tumor mechanisms of fullerenes and summarizes the most recent works on the functionalization of fullerenes and the application of fullerene derivatives in tumor treatment. This review aims to serve as a valuable reference for further development and clinical application of anti-tumor fullerene derivatives.

Evodiamine (EVO) is a tryptamine indole alkaloid and the main active ingredient in Evodia rutaecarpa. In recent years, the antitumor, cardioprotective, anti-inflammatory, and anti-Alzheimer's disease effects of EVO have been reported. EVO exerts antitumor effects by inhibiting tumor cell activity and proliferation, blocking the cell cycle, promoting apoptosis and autophagy, and inhibiting the formation of the tumor microvasculature. However, EVO has poor solubility and low bioavailability. Several derivatives with high antitumor activity have been discovered through the structural optimization of EVO, and new drug delivery systems have been developed to improve the solubility and bioavailability of EVO. Current research found that EVO could have toxic effects, such as hepatotoxicity, nephrotoxicity, and cardiac toxicity. This article reviews the pharmacological activity, derivatives, drug delivery systems, toxicity, and pharmacokinetics of EVO and provides research ideas and references for its further in-depth development and clinical applications.

Background: Autoimmune hepatitis (AIH) is a serious liver disease characterized by immune disorders, particularly effector T-cell overactivation. This study aimed to explore the therapeutic effect and underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment on CD4⁺ T-cell overactivation and liver injury in AIH.

Methods: The metabolic changes of CD4⁺ T cells were assayed in human AIH and mouse hepatitis models. The liver protective effect of MSC-EVs was evaluated by transaminase levels, liver histopathology and inflammation. The effect of MSC-EVs on the metabolic state of CD4⁺ T cells was also explored.

Results: Enhanced glycolysis (eg, ~1.5-fold increase in hexokinase 2 levels) was detected in the CD4⁺ T cells of AIH patient samples and mouse hepatitis models, whereas the inhibition of glycolysis decreased CD4⁺ T-cell activation (~1.8-fold decrease in CD69 levels) and AIH liver injury (~6-fold decrease in aminotransferase levels). MSC-EV treatment reduced CD4⁺ T-cell activation (~1.5-fold decrease in CD69 levels) and cytokine release (~5-fold decrease in IFN-γ levels) by reducing glycolysis (~3-fold decrease) while enhancing mitochondrial oxidative phosphorylation (~2-fold increase in maximal respiration) in such cells. The degree of liver damage in AIH mice was ameliorated after MSC-EV treatment (~5-fold decrease in aminotransferase levels). MSC-EVs carried abundant mitochondrial proteins and might transfer them to metabolically reprogram CD4⁺ T cells, whereas disrupting mitochondrial transfer impaired the therapeutic potency of MSC-EVs in activated CD4⁺ T cells.

Conclusion: Disordered glucose metabolism promotes CD4⁺ T-cell activation and associated inflammatory liver injury in AIH models, which can be reversed by MSC-EV therapy, and this effect is at least partially dependent on EV-mediated mitochondrial protein transfer between cells. This study highlights that MSC-EV therapy may represent a new avenue for treating autoimmune diseases such as AIH.

Introduction: Oligonucleotide (ON) therapy is a promising treatment for a wide range of complex genetic disorders, but inefficient intracellular ON delivery has hindered clinical translation. Hollow silica nanoparticles (HSN) hold potential as effective ON delivery vehicles since ON can be encapsulated in the hollow core in situ where they are protected from degradation by eg nucleases. However, HSN must be modified to allow degradation and subsequent (sub)cellular ON release. In this report, we investigated the use of ion and fluorescent dye co-doping in the HSN silica matrix to enable HSN degradability and in vitro visualization.

Methods: HSN were core encapsulated with ON, doped with Ca²⁺, Cu²⁺, Zn²⁺, Se²⁺ and Sr²⁺ ions and co-condensed with rhodamine b isothiocyanate (RITC) by a modified reverse microemulsion method. HSN were physiochemically characterized and their biological activity such as uptake and toxicity were evaluated in mesenchymal stem cells (hMSCs).

Results: We successfully doped HSN with RITC and Ca²⁺, Cu²⁺, Zn²⁺ and Sr²⁺ ions. We observed that doping HSN with Ca²⁺ and Sr²⁺ enhanced RITC incorporation while ON encapsulation in HSN increased Cu²⁺ and Zn²⁺ doping efficiency. Moreover, our dual-doped HSN demonstrated controlled ON release in the presence of intracellular mimicking levels of glutathione (GSH) and limited release in the absence of GSH over 14 days. HSN were biocompatible in hMSCs up to 300 µg/mL except for Cu²⁺ doped HSNs which were cytotoxic even at ~10 µg/mL. HSN uptake was influenced by the dopant ion, DNA encapsulation, and HSN concentration, where Zn-HSN showed the lowest and Sr-HSN and Se-HSN_D, the highest uptake in hMSCs.

Conclusion: We report a straightforward one-pot procedure to create ion and fluorescent dye co-doped HSN that can efficiently incorporate ON, as promising new gene vectors.