International Journal of Nanomedicine最新文献

The escalating threat of antibiotic-resistant bacteria, particularly those forming biofilm structures, underscores the urgent need for alternative treatment strategies. Bacteriophages have emerged as promising agents for combating bacterial infections, especially those associated with biofilm formation. However, the efficacy of phage therapy can be limited by the development of bacterial resistance and biofilm regrowth. Interestingly, phages could be combined with other agents, such as metal nanoparticles, to enhance their antibacterial effectiveness. Since the therapeutic strategy of using phages and metal nanoparticles has been developed relatively recently, evaluating its efficacy under various conditions is essential, with a particular focus on the duration of activity. This study tested the hypothesis that a novel approach to combating bacterial biofilms, based on phages armed with silver nanoparticles (AgNPs), would exhibit enhanced activity over an extended period after application. In this work, we investigated the potential of engineered T7 phages armed with AgNPs for eradicating Escherichia coli biofilm. We demonstrated that such biomaterial exhibits sustained antimicrobial activity even after prolonged exposure. Compared to phages alone or AgNPs alone, the biomaterial significantly enhances biofilm eradication, particularly after 48 hours of treatment. These findings highlight the potential of synergistic phage-nanoparticle strategies for combatting biofilm-associated infections.

Immunotherapy is a promising cancer treatment because of its ability to sustainably enhance the natural immune response. However, the effects of multiple immunotherapies, including ICIs, are limited by resistance to these agents, immune-related adverse events, and a lack of reasonable therapeutic targets available at the right time and place. The tumor microenvironment (TME), which features tumor-associated macrophages (TAMs), plays a significant role in resistance owing to its hypoxic microenvironment and lack of blood vessels, resulting in cancer immune evasion. To enhance immunotherapy, photodynamic therapy (PDT) can increase innate and adaptive immune responses through immunogenic cell death (ICD) and improve the TME. Traditional photosensitizers (PSs) also include novel nanomedicines to precisely target tumor cells or TAMs. Here, we reviewed and summarized current strategies and possible influencing factors for nanomedicines for cancer photoimmunotherapy.

Given the global prevalence of prostate cancer in men, it is crucial to explore more effective treatment strategies. Recently, immunotherapy has emerged as a promising cancer treatment due to its unique mechanism of action and potential long-term effectiveness. However, its limited efficacy in prostate cancer has prompted renewed interest in developing strategies to improve immunotherapy outcomes. Nanomedicine offers a novel perspective on cancer treatment with its unique size effects and surface properties. By employing targeted delivery, controlled release, and enhanced immunogenicity, nanoparticles can be synergized with nanomedicine platforms to amplify the effectiveness of immunotherapy in treating prostate cancer. Simultaneously, nanotechnology can address the limitations of immunotherapy and the challenges of immune escape and tumor microenvironment regulation. Additionally, the synergistic effects of combining nanomedicine with other therapies offer promising clinical outcomes. Innovative applications of nanomedicine include smart nanocarriers, stimulus-responsive systems, and precision medicine approaches to overcome translational obstacles in prostate cancer immunotherapy. This review highlights the transformative potential of nanomedicine in enhancing prostate cancer immunotherapy and emphasizes the need for interdisciplinary collaboration to drive research and clinical applications forward.

Purpose: Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4-8°C) likely influences the organism's blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM.

Methods: The effects of CT (4-8°C) or room temperature (RT, 22-25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot.

Results: CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting β-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect.

Conclusion: Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.

Object: The present study intended to evaluate the effect of simvastatin-loaded nanomicelles (SVNs) on promoting new bone formation and reducing alveolar ridge resorption at the tooth extraction sites at the early healing of the extraction sockets.

Methods: SVNs were synthesized using a dialysis method. The rabbit tooth extraction model was established, SVNs and simvastatin (SV) were loaded on gelatin sponge and inserted into the extraction socket. CBCT scans were performed at 0, 2, and 4 weeks postoperatively to evaluate bone formation and alveolar ridge absorption in the extraction sockets. And all the animals were sacrificed and the mandibles were harvested. And HE staining and Masson staining were used for histological evaluation of the bone formation in the extraction sockets.

Results: Radiographic evaluation showed that compared with the blank control group, at 2 and 4 weeks after extraction, SVNs increased the new bone density in the extraction sockets by 75.7% and 96.5%, and reduced the absorption rate of alveolar ridge length at the extraction sites by 60.8% and 49.1%, respectively. Histological evaluation showed that SVNs significantly improved the maturation of new bone tissue in the extraction sockets.

Conclusion: SVNs can significantly accelerate healing and effectively reduce the absorption of alveolar ridge at the extraction sites in the early stage of tooth extraction socket healing.

Background: Tumor development and progression is a long and complex process influenced by a combination of intrinsic (eg, gene mutation) and extrinsic (eg, environmental pollution) factors. As a detoxification organ, the liver plays an important role in human exposure and response to various environmental pollutants including nanomaterials (NMs). Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and remains a serious threat to human health. Whether NMs promote liver cancer progression remains elusive and assessing long-term exposure to subtoxic doses of nanoparticles (NPs) remains a challenge. In this study, we focused on the promotional effects of nano zinc oxide (nZnO) on the malignant progression of human HCC cells HepG2, especially aged nZnO that has undergone physicochemical transformation.

Methods: In in vitro experiments, we performed colony forming efficiency, soft agar colony formation, and cell migration/invasion assays on HepG2 cells that had been exposed to a low dose of nZnO (1.5 μg/mL) for 3 or 4 months. In in vivo experiments, we subcutaneously inoculated HepG2 cells that had undergone long-term exposure to nZnO for 4 months into BALB/c athymic nude mice and observed tumor formation. ZnCl₂ was administered to determine the role of zinc ions.

Results: Chronic low-dose exposure to nZnO significantly intensified the malignant progression of HCC cells, whereas aged nZnO may exacerbate the severity of malignant progression. Furthermore, through transcriptome sequencing analysis and in vitro cellular rescue experiments, we demonstrated that the mechanism of nZnO-induced malignant progression of HCC could be linked to the activation of Claudin-2 (CLDN2), one of the components of cellular tight junctions, and the dysregulation of its downstream signaling pathways.

Conclusion: Long-term exposure of fresh and aged nZnO promotes hepatocellular carcinoma malignancy by up-regulating CLDN2. The implications of this work can be profound for cancer patients, as the use of various nanoproducts and unintentional exposure to environmentally transformed NMs may unknowingly hasten the progression of their cancers.

Polyethylene glycol (PEG)-modified nanoparticles (NPs) often struggle with reduced effectiveness against metastasis and liquid tumors due to limited tumor cell uptake and therapeutic efficacy. To address this, actively targeted liposomes with enhanced tumor selectivity and internalization are being developed to improve uptake and treatment outcomes. Using bi-functional proteins to functionalize PEGylated NPs and enhance targeted drug delivery through non-covalent attachment methods has emerged as a promising approach. Among these, the one-step and two-step targeting strategies stand out for their simplicity, efficiency, and versatility. The one-step strategy integrates streptavidin-tagged antibodies or bispecific antibodies (bsAbs: PEG/DIG × marker) directly into PEGylated NPs. This method uses the natural interactions between antibodies and PEG for stable, specific binding, allowing the modification of biotin/Fc-binding molecules like protein A, G, or anti-Fc peptide. Simply mixing bsAbs with PEGylated NPs improves tumor targeting and internalization. The two-step strategy involves first accumulating bsAbs (PEG/biotin × tumor marker) on the tumor cell surface, triggering an initial attack via antibody-dependent and complement-dependent cytotoxicity. These bsAbs then capture PEGylated NPs, initiating a second wave of internalization and cytotoxicity. Both strategies aim to enhance the targeting capabilities of PEGylated NPs by enabling specific recognition and binding to disease-specific markers or receptors. This review provides potential pathways for accelerating clinical translation in the development of targeted nanomedicine.

Purpose: Non-alcoholic fatty liver disease (NAFLD) represents a significant global health burden, exhibiting a strong correlation with insulin resistance, obesity, and type 2 diabetes (T2DM). Despite the severity of hepatic steatosis in T2DM patients, no specific drugs have been approved for clinical treatment of the disease. Tangerine peel is one kind of popular functional food and reported to possess hypoglycemic and lipid-lowering potential. In this study, we investigated the effects of Tangerine-peel-derived exosome-like nanovesicles (TNVs) on hepatic lipotoxicity associated with T2DM.

Methods: The TNVs was prepared by differential centrifugation of the aqueous extract of Tangerine and chemical properties were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and LC-MS/MS. The hypoglycemic and lipid-lowering potential of TNVs were possessed by biochemical measurement, RT-PCR, 16S rRNA sequencing, GC/MS, UHPLC-MS/MS, in vivo small animal imaging assay and HE staining. Subsequently, effects of TNVs on lipid accumulation and glycolysis were investigated on 3T3-L1 and AML-12 cells.

Results: TNVs significantly inhibited insulin resistance, reduced hepatic lipid accumulation, facilitate intestinal mucosal repair, rescued gut microbiota dysbiosis, regulated colonic SCFA and liver bile acid metabolism in db/db mice. Furthermore, TNVs restored the expression of key genes in glucose and lipid metabolism (ACC, AMPK, CD36, LXRα, PPAR-γ, SREBP-1) while activating the expression of genes related to glycolysis (G6Pase, GLUT2, PCK1, PEPCK) in db/db mice. Further cell-based mechanistic studies revealed that TNVs reduced lipid accumulation in 3T3-L1 and AML-12 cells via regulation of glucose and lipid metabolism-related genes (UCP1, FGFR4, PRDM16, PGC-1α, Tmem26, Cpt1, Cpt2 and PPAR-α).

Conclusion: We for the first time demonstrated that TNVs could significantly improve glucose and lipid metabolism via activating the expression of genes related to fatty acid β-oxidation and glycolysis.

Background: Colorectal cancer (CRC) has become a significant global public health challenge, demanding immediate attention due to its high incidence and mortality rates. Regular CRC screening is essential for the early detection of precancerous lesions and CRC.

Methods: : We developed a novel surface-enhanced Raman scattering (SERS) analysis platform that employs high-throughput microarray chips as carriers and Au/SnO₂ nanoring arrays (Au/SnO₂ NRAs) as substrates. This platform utilizes an aptamer recognition-release strategy to achieve efficient and sensitive detection of protein tumor markers. In the detection process, the strong affinity and high specificity between the aptamer and the target protein result in competitive replacement of the SERS nanoprobes originally bound to the substrate surface. As a result, the SERS nanoprobes carrying Raman reporter genes are dislodged, leading to a reduction in the SERS signal intensity.

Results: The platform demonstrated excellent detection performance, with rapid detection completed within 15 minutes and limits of detection (LOD) as low as 6.2×10^-12 g/mL for hnRNP A1 and 6.51×10^-12 g/mL for S100P. Clinical samples analyzed using the SERS platform showed high consistency with enzyme-linked immunosorbent assay (ELISA) results.

Conclusion: This platform offers strong support for the early detection, risk assessment, and treatment monitoring of colorectal cancer precancerous lesions, with broad potential for clinical applications.

Introduction: Breast cancer ranks among the most prevalent cancers in women, characterized by significant morbidity, disability, and mortality. Presently, chemotherapy is the principal clinical approach for treating breast cancer; however, it is constrained by limited targeting capability and an inadequate therapeutic index. Photothermal therapy, as a non-invasive approach, offers the potential to be combined with chemotherapy to improve tumor cellular uptake and tissue penetration. In this research, a mesoporous polydopamine-coated gold nanorod nanoplatform, encapsulating doxorubicin (Au@mPDA@DOX), was developed.

Methods: This nanoplatform was constructed by surface coating mesoporous polydopamine (mPDA) onto gold nanorods, and doxorubicin (DOX) was encapsulated in Au@mPDA owing to π-π stacking between mPDA and DOX. The dynamic diameter, zeta potential, absorbance, photothermal conversion ability, and drug release behavior were determined. The cellular uptake, cytotoxicity, deep penetration, and anti-tumor effects were subsequently investigated in 4T1 cells. After that, fluorescence imaging, photothermal imaging and pharmacodynamics studies were utilized to evaluate the anti-tumor effects in tumor-bearing mice model.

Results: This nanoplatform exhibited high drug loading capacity, excellent photothermal conversion and, importantly, pH/photothermal dual-responsive drug release behavior. The in vitro results revealed enhanced photothermal-facilitated cellular uptake, drug release and tumor penetration of Au@mPDA@DOX under near-infrared irradiation. In vivo studies confirmed that, compared with monotherapy with either chemotherapy or photothermal therapy, the anti-tumor effects of Au@mPDA@DOX are synergistically improved.

Conclusion: Together with good biosafety and biocompatibility, the Au@mPDA@DOX nanoplatform provides an alternative method for safe and synergistic treatment of breast cancer.