International Journal of Nanomedicine最新文献

Different types of cancers affect the gastrointestinal tract (GIT), starting from the oral cavity and extending to the colon. In general, most of the current research focuses on the systemic delivery of the therapeutic agents, which leads to undesired side effects and a limited enhancement in the therapeutic outcomes. As a result, localized delivery within gastrointestinal (GI) cancers is favorable in overcoming these limitations. However, the localized delivery via oral administration faces many challenges related to the complex structure of GIT (varied pH levels and transit times) as well as the harsh environment within tumor cells (hypoxia, efflux pumps, and acidity). To overcome these obstacles, nano-drug delivery systems (NDDs) have been designed and proved their potential by exploiting these challenges in favor of offering a specific delivery to the desired target. The current review begins with an overview of different GI cancers and their impact globally. Then, it discusses the current treatment approaches and their corresponding limitations. Additionally, the different challenges associated with localized drug delivery for GI cancers are summarized. Finally, the review discusses in detail the recent therapeutic and diagnostic applications of NDDs that have been conducted in oral, esophageal, gastric, colon, and liver cancers, aiming to offer valuable insights into the current and future state of utilizing NDDs for the local treatment of GI cancers.

Purpose: The purpose of this study is to develop an innovative solution for chronic wounds in high-mobility areas, such as joints, where conventional treatments are hindered by passive healing mechanisms and the need for immobilization. By designing a micro-electro-Nanofiber dressing composed of piezoelectric polyvinylidene fluoride (PVDF) integrated with antimicrobial silver nanoparticles (AgNPs), this research aims to address the dual challenges of promoting effective wound healing and maintaining joint mobility.

Methods: Herein, we developed a novel micro-electro-Nanofiber dressing using electrospinning technology, incorporating polyvinylidene fluoride (PVDF) with silver nanoparticles (AgNPs). The optimized PVDF-AgNPs Nanofiber dressings exhibited strong piezoelectric effects suitable for joint wounds.

Results: In vitro experiments demonstrated that the dressing effectively promoted fibroblast migration and collagen synthesis. In vivo, the dressing exhibited a trend of rapid healing in infected wounds within 12 days while modulating macrophage differentiation toward the anti-inflammatory M2 phenotype. Additionally, the incorporation of antimicrobial nanosilver effectively controlled local infections, further facilitating the healing process.

Conclusion: To sum up, by harnessing the piezoelectric effect to stimulate endogenous healing mechanisms without restricting joint mobility, the developed PVDF-AgNPs Nanofiber dressings represent a transformative approach for the treatment of wounds in highly mobile body areas.

The metabolic activity of tumor cells leads to the acidification of the surrounding microenvironment, which provides new strategies for the application of nanotechnology in cancer therapy. Researchers have developed various types of pH-responsive nanomaterials based on the tumor acidic microenvironment. This review provides an in-depth discussion on the design mechanisms, drug-loading strategies, and application pathways of tumor acidic microenvironment-responsive nanodrug delivery systems. These materials trigger drug release upon reaching the tumor microenvironment, enhancing therapeutic targeting and reducing toxicity to healthy cells. pH-responsive nanomaterials include organic nanomaterials, inorganic nanomaterials, and composite nanomaterials. Additionally, this review outlines the drug-loading strategies, application prospects, and challenges of pH-responsive nanomaterials, aiming to promote the development and clinical translation of this field.

Background: Exosomes sourced from mesenchymal stem cells (MSC-EXOs) have become a promising therapeutic tool for sepsis-induced myocardial dysfunction (SMD). Our previous study demonstrated that Apelin pretreatment enhanced the therapeutic benefit of MSCs in myocardial infarction by improving their paracrine effects. This study aimed to determine whether EXOs sourced from Apelin-pretreated MSCs (Apelin-MSC-EXOs) would have potent cardioprotective effects against SMD and elucidate the underlying mechanisms.

Methods: MSC-EXOs and Apelin-MSC-EXOs were isolated and identified. Mice neonatal cardiomyocytes (NCMs) were treated with MSC-EXOs or Apelin-MSC-EXOs under lipopolysaccharide (LPS) condition in vitro. Cardiomyocyte pyroptosis was determined by TUNEL staining. RNA sequencing was used to identify differentially expressed functional miRNAs between MSC-EXOs and Apelin-MSC-EXOs. MSC-EXOs and Apelin-MSC-EXOs were transplanted into a mouse model of SMD induced by cecal ligation puncture (CLP) via the tail vein. Heart function was evaluated by echocardiography.

Results: Compared with MSC-EXOs, Apelin-MSC-EXO transplantation greatly enhanced cardiac function in SMD mice. Both MSC-EXOs and Apelin-MSC-EXOs suppressed cardiomyocyte pyroptosis in vivo and in vitro, with the latter exhibiting superior protective effects. miR-34a-5p effectively mediated Apelin-MSC-EXOs to exert their cardioprotective effects in SMD with high mobility group box-1 (HMGB1) as the potential target. Mechanistically, Apelin-MSC-EXOs delivered miR-34a-5p into injured cardiomyocytes, thereby ameliorating cardiomyocyte pyroptosis via regulation of the HMGB1/AMPK axis. These cardioprotective effects were partially abrogated by downregulation of miR-34a-5p in Apelin-MSC-EXOs.

Conclusion: Our study revealed miR-34a-5p as a key component of Apelin-MSC-EXOs that protected against SMD via mediation of the HMGB1/AMPK signaling pathway.

Purpose: None of the antibody-drug conjugates (ADCs) targeting Claudin 18.2 (CLDN18.2) have received approval from regulatory authorities due to their limited clinical benefits. Leveraging the radiosensitizing ability of Deruxtecan (DXd) and the internal radiation therapy of ¹³¹I for tumors, we aimed to develop the first radio-antibody-drug conjugates (RADCs) for the treatment of gastric cancer.

Methods: The CLDN18.2-specific antibody HLX58 was conjugated with the payload DXd through a cleavable maleimide glycynglycyn-phenylalanyn-glycyn (GGFG) peptide linker. HLX58-Der was labeled with ¹³¹I to produce RADC-¹³¹I-HLX58-Der. HLX58 was labeled with ¹²⁵I for imaging CLDN18.2-positive tumors, providing a reference for RADC treatment in solid tumors. The antigen-binding properties and biodistribution of the RADC were studied both in vitro and in vivo. The cytotoxic effects of the RADC were evaluated in CLDN18.2-positive tumor cell lines and xenografts.

Results: HLX58 was successfully conjugated with DXd using the cleavable maleimide GGFG peptide linker and labeled with ¹³¹I to produce RADC-¹³¹I-HLX58-Der. HLX58 was labeled with ¹²⁵I for imaging CLDN18.2-positive tumors. Both ¹²⁵I-HLX58 and ¹³¹I-HLX58-Der exhibited significant binding affinity for the CLDN18.2-positive cancer cell line. The cytotoxic effect of ¹³¹I-HLX58-Der was observed in the CLDN18.2-positive cell line, with an IC₅₀ of 11.28 ng/mL. In terms of cytotoxicity, ¹³¹I-HLX58-Der exhibited greater activity compared to HLX58-Der. ¹²⁵I-HLX58 and ¹³¹I-HLX58-Der demonstrated similar biodistribution profiles in CLDN18.2-positive tumor models, achieving 5.72 ± 0.41%ID/g (48 h) and 5.83 ± 0.41%ID/g (72 h) in the tumor tissues postinjection, respectively. The average tumor size in groups treated with ¹³¹I-HLX58-Der and HLX58-Der was reduced by factors of 12.15 and 4.80, respectively, compared to the control group. ¹³¹I-HLX58-Der demonstrated no toxic effects on hepatorenal function, routine blood tests, or major organs in mice when compared to the control group.

Conclusion: These findings validate the potential of RADCs targeting CLDN18.2 in treating CLDN18.2-expressing solid tumors.

Purpose: Outer membrane vesicles (OMVs) derived from Gram-negative bacteria naturally serve as a heterologous nano-engineering platform, functioning as effective multi-use nanovesicles for diagnostics, vaccines, and treatments against pathogens. To apply refined OMVs for human theranostic applications, we developed naturally exposed receptor-binding domain (RBD) OMVs grafted with antigen 43 as a minimal modular system targeting angiotensin-converting enzyme 2 (ACE2).

Methods: We constructed E. coli-derived OMVs using the antigen 43 autotransporter system to display RBD referred to as viral mimetic Ag43β700_RBD OMVs. Based on this, Ag43β700_RBD protein were expressed onto Escherichia coli (E. coli) membrane. Artificial viral mimetic Ag43β700_RBD OMVs were fabricated by self-assembly through membrane disruption of the Ag43β700_RBD E. coli using a chemical detergent mainly containing lysozyme. Through serial centrifugation to purify fabricated OMVs, spherical Ag43β700_RBD OMVs with an average diameter of 218 nm were obtained. The confirmation of the RBD expressed on OMVs was performed using trypsin treatment.

Results: Our viral mimetic Ag43β700_RBD OMVs had an impact on the theranostic studies: (i) angiotensin-converting enzyme 2 blockade assay, (ii) enzyme-linked immunosorbent assay for the OMVs, and (iii) intracellular uptake and neutralization assay. As serodiagnostic surrogates, Ag43β700_RBD OMVs were applied to ACE2 blockade and OMVs-ELISA assay to quantify neutralization antibodies (nAbs). They reduced the robust immune response in vitro, especially IL-6 and IL-1β. Experiments in mice, Ag43β700_RBD OMVs was successfully proven to be safe and effective; they produced a detectable level of nAbs with 39-58% neutralisation and reduced viral titres in the lungs and brain without weight loss.

Conclusion: The developed viral mimetic Ag43β700_RBD OMVs may therefore be applied as a nanovesicle-theranostic platform for further emerging infectious disease-related diagnosis, vaccination, and treatment.

Introduction: Androgenetic alopecia (AGA) is a multifactorial and age-related dermatological disease that affects both males and females, usually at older ages. Traditional hair repair drugs exemplified by minoxidil have limitations such as skin irritation and hypertrichosis. Thus, attention has been shifted to the use of repurposing drugs. Metformin is an anti-diabetic drug, that can promote hair follicle regeneration via upregulation of the hair-inductive capability. Hence, the current study aims to fabricate a safe and effective nanoemulsion to improve metformin efficacy in targeting AGA.

Methods: Rosemary oil was selected as the oily phase due to its ability to increase blood flow and hair growth. Rosemary-based nanoemulsions were statistically optimized by Box-Behnken experimental design, loaded with metformin, and incorporated into a hydrogel to form a nanoemulgel. Metformin-loaded nanoemulsions were assessed for their diametric size, uniformity, zeta potential, and metformin characteristics within the formulated nanosystem. The nanoemulgel was then evaluated in terms of its pH, percentage drug content, and in-vitro release performance. In-vivo study assessed the nanoemulgel's ability to augment hair growth in rats.

Results: The experimental design displayed that using 50%w/w, 20%w/w, and 10%w/w of Cremophor^®, Labrafil^®, and deionized water, respectively, resulted in nanoemulsion formulation with the smallest globule size (125.01 ± 0.534 nm), unimodal size distribution (PDI=0.103), negative surface charge (-19.9 ± 2.01 mV) with a spherical morphological structure. Rosemary-based nanoemulgel displayed acceptable physicochemical characterizations namely; a neutral pH value of 6.7±0.15, high drug content (92.9± 2.3%), and controlled metformin in-vitro release. Besides, the formulated nanoemulgel significantly increased the number of hair follicles in the animal model compared with other controls and tested groups.

Conclusion: The designed nanoemulgel is a promising approach for treating androgenic alopecia.

Glioma is the most common primary malignant brain tumor with a poor survival rate. It is characterized by diffuse and invasive growth and heterogeneity, which limits tumor identification and complete resection. Therefore, the precise detection and postoperative adjuvant therapy of gliomas have become increasingly important and urgent. Nanotechnology, with its excellent biocompatibility and controllable chemical properties, has attracted much attention in recent decades. Metal nanoparticles are widely used in the field of biomedical imaging and detection, and have shown promising applications in targeted drug delivery and therapy. The current review aims to systematically summarize the application of different types of metal nanoparticles in the treatment and detection of glioma. We also discussed the advantages and mechanisms of metal nanoparticles when used for glioma therapy, including chemotherapy, radiotherapy and photothermal therapy. We hope to promote the application of metallic nanoparticles in glioma diagnosis and treatment, moving towards clinical translation to benefit patients.

In recent years, with an increasingly profound comprehension of the tumor microenvironment, it has been discovered that the constituent cells within the immune microenvironment, such as macrophages, CD4⁺T cells, and CD8⁺T cells, interact with tumor cells in manners conducive to tumorigenesis and progression. Exosomes play a pivotal role as essential mediators for intercellular material exchange and signal transmission in this context. Tumor cell-derived exosomes carrying cargo such as PD-L1 and ncRNAs engage with CD8⁺T cells to induce cytotoxic responses and facilitate immune evasion, thereby promoting tumor advancement. When combined with current immune checkpoint inhibitors like anti-PD-L1/PD-1 therapy, enhancing CD8⁺T cell function through exosomal pathways while monitoring and augmenting therapeutic effects can significantly improve efficacy. This review delineates the crucial role of exosomes derived from both tumor cells and CD8⁺T cells within the tumor microenvironment along with their impact mechanisms on both tumor cells and CD8⁺T cells. Furthermore, it summarizes the potential for clinical treatment in this realm when integrated with existing immunotherapy methods-particularly exploring the feasibility of clinical translation alongside engineering materials science techniques.