International Journal of Nanomedicine最新文献

Background: Precise intraoperative tumor delineation is essential for successful surgical outcomes. However, conventional methods are often incompetent to provide intraoperative guidance due to lack specificity and sensitivity. Recently fluorescence-guided surgery for tumors to delineate between cancerous and healthy tissues has attracted widespread attention. The contrast-enhanced fluorescent imaging has been applied for non-invasive diagnosis of cancers using tumor-targeting fluorescent probes.

Methods: The carbonic anhydrase IX targeted polyaspartamide fluorescent compounds (SD-PHEA-NI) were synthesized by incorporating a tumor-targeting group of sulfadiazine (SD) and N-butyl-4-ethyldiamino-1,8-naphthalimide (NI) into water-soluble carriersof poly-α,β-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA). These derivatives were also characterized by Fourier transform infrared spectroscopy, gel permeation chromatography, ultraviolet-visible spectroscopy, nuclear magnetic resonance spectroscopy and fluorescence assays. The cellular uptake, cytotoxicity, and fluorescence imaging ability were evaluated.

Results: Experiment results indicated that SD-PHEA-NI has low cytotoxic to Henrietta Lacks (HeLa) cells. Moreover, B16F10 melanoma cells can take up SD-PHEA-NI and show good green fluorescent images. However, SD-PHEA-NI displayed a low-intensity green fluorescence signal in healthy human embryonic kidney (293T) cells.

Conclusion: SD-PHEA-NI can be considered a potential fluorescent probe for the detection of tumors. This study has the potential to enhance tumor diagnosis and image-guided surgical interventions by providing real-time information and robust decision support, thereby reducing recurrence and complication rates and ultimately improving patient outcomes.

Introduction: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration. Chondrocyte inflammation, apoptosis, and extracellular matrix degradation accelerated OA progression. MicroRNA (miRNA) has the potential to be a therapeutic method for osteoarthritis. However, it is difficult to penetrate the cell to exercise its biological function, and its extracellular effect is unclear.

Methods: lipo-AgPEI-miR-200c-3p was created by combining miR-200c-3p with silver nitrate polyvinylimine nanoparticles on a microfluidic device. The drug release curve, stability, temperature sensitivity, cytotoxicity, and the impact of lipo-AgPEI-miR-200c-3p on the expression of proteins linked to matrix disintegration, apoptosis, and inflammatory factors were all detected.

Results: Results showed that the particle size of Lipo-AgPEI-miR-200c-3p was about 130 nm, the Zeta potential was lowered to 1.08±0.12 mV. Lipo-AgPEI-miR-200c-3p could increase cell viability, prevent cell apoptosis, and decrease the expression levels of TNF-α, IL-6, IL-1β, and MCP-1 in ADTC5 cells following LPS stimulation. MMP3, MMP13, and ADAMTS-4 expression was downregulated whereas collagen II expression was upregulated. The ZEB2 expression was greatly elevated following LPS stimulation and dramatically decreased following transfection of miR-200c-3p. Collagen II expression rose following transfection of si-ZEB2, whereas the expression levels of inflammatory factors, apoptosis-related proteins, MMP3, MMP13, and ADAMTS-4 decreased. The dual luciferase experiment demonstrated that ZEB2 was the target gene of miR-200c-3p.

Conclusion: The synergistic effect of AgPEI and miR-200c-3p can inhibit the inflammatory response, apoptosis, and matrix degradation of chondrocytes. Lipo-AgPEI-miR-200c-3p can also improve transfection efficiency and obtain good physicochemical properties of drugs. miR-200c-3p may be crucial in the development of OA and can influence the target gene ZEB2, control the inflammatory response, apoptosis, and chondrocyte matrix breakdown.

Background: Given the risks associated with autologous bone transplantation and the limitations of allogeneic bone transplantation, scaffolds in bone tissue engineering that incorporate bioactive peptides are highly recommended. Teriparatide (TPTD) plays a significant role in bone defect repair, although achieving controlled release of TPTD within a bone tissue engineering scaffold remains challenging. This work reports a new approach for treatment of teriparatide using a water-in-oil-in-water (w/o/w) microspheres be equipped on gelatin (GEL)/Poly lactic-glycolic acid (PLGA)/attapulgite (ATP) scaffold.

Methods: In this study, TPTD microspheres were prepared by the water-in-oil-in-water (w/o/w) double emulsion technique and GEL/PLGA/ATP composite scaffolds with different setups were prepared by salt leaching method. Both microspheres and scaffolds underwent physicochemical characterization. Mouse bone mesenchymal stem cells (BMSCs) were co-cultured with extracts from the microspheres and scaffolds to evaluate cell proliferation and osteogenesis. Four weeks post-implantation, the effectiveness of the scaffolds containing microspheres for repairing skull defects in mice was assessed.

Results: Both TPTD microspheres and the GEL/PLGA/ATP scaffold significantly enhanced the proliferation and osteogenic differentiation of BMSCs. Markers of osteoblast activity, including COL1, RUNX2, OCN, and OPN, were markedly up-regulated. Further, micro-CT, histological, and immunohistochemical analyses revealed extensive new bone formation on the scaffold.

Conclusion: The GEL/PLGA/ATP composite scaffold, equipped with TPTD microspheres, demonstrates significant potential for use in bone tissue engineering, providing an effective option for bone regeneration and repair in clinical applications.

Objective: The difficulty of establishing slow release at intestinal infection sites, weak antibacterial effects, as well as the limited broad use of florfenicol oral formulations are the main targets of the current study. Novel hydrogels derived from sodium alginate were developed using a complexation form for florfenicol delivery to achieve slow release at the site of intestinal infection and enhance its antibacterial activity against Escherichia coli.

Methods: The optimal formulation, physicochemical properties, stability, pH-responsive performance, antibacterial activity, and in vitro biosafety of the florfenicol hydrogels have been studied systematically.

Results: The created hydrogels had a consistent spherical morphology, with an average diameter of 531.9±12.6 nm. Energy dispersive spectroscopy and Fourier transform infrared indicated that florfenicol hydrogels have been successfully prepared through complexation force. Furthermore, it is shown that florfenicol hydrogels hold outstanding stability, excellent sustained release, and faster swelling and release at intestinal pH due to pH-responsiveness. The florfenicol hydrogels had no obvious structural destruction in simulated gastric juice (pH=1.2) for 12 hrs and were highly stable. However, the hydrogels began to be destroyed after 5 minutes in simulated intestinal fluid (SIF), and this decomposition was continuous. With the decomposition of the structure of florfenicol hydrogels, the encapsulated florfenicol was also slowly released, and thus, it achieves the slow-release effect. Additionally, the florfenicol hydrogels showed a low hemolytic ratio and greater antibacterial activity compared with florfenicol.

Conclusion: The blended formulation creates a promising oral matrix intended for the slow-release of florfenicol along the gastrointestinal tract.

Background: Antibiotic resistance of many bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA), has become a major threat to global health. Zinc Oxide Quantum dots (ZnO-QDs) show good antibacterial activity, but most of them are insoluble in water, limiting their application range, and there is a lack of research on drug resistance inducement.

Methods: The water-soluble zinc oxide quantum dots modified by APTES (ZnO@APTES QDs) were prepared by a microwave assisted synthesis. Then ZnO@APTES QDs were characterized through various methods. After confirmation of synthesized ZnO@APTES QDs, its bactericidal effect on MRSA was detected through in vitro and in vivo experiments, and its mechanism of action was analyzed.

Results: Characterization analysis revealed that the ZnO@APTES QDs have a particle size of 5 nm. The minimum inhibitory concentrations (MIC) were determined to be 64 µg mL^-1 for Escherichia coli (E. coli) and 32 µg mL^-1 for MRSA. The ZnO@APTES QDs showed significant inhibition of MRSA biofilm formation and effectively disrupted mature biofilms. Notably, the ZnO@APTES QDs did not induce tolerance or resistance even after 30 days of repeated exposure, whereas antibiotics led to a rise in bacterial MIC within 3 days and a 60-fold increase after 30 days. Mechanistic analysis indicated that the positively charged quantum dots interact with bacterial surfaces, altering membrane fluidity. Once inside the bacteria, the ZnO@APTES QDs generate reactive oxygen species (ROS), causing DNA damage and bacterial cell death. Moreover, the ZnO@APTES QDs possessed good biocompatibility and demonstrated significant therapeutic efficacy against drug-resistant bacterial infections in both macrophage and mouse wound infection models.

Conclusion: In summary, we have synthesized a highly effective water-soluble ZnO@APTES QDs that shows strong antibacterial and therapeutic efficacy against MRSA and other bacteria. The ZnO@APTES QDs holds significant potential for development as a new treatment agent for combating antibiotic-resistant infections.

Purpose: Cardiac fibrosis, a key contributor to ventricular pathologic remodeling and heart failure, currently lacks effective therapeutic approaches.

Patients and methods: Small extracellular vesicles from young healthy human plasma (Young-sEVs) were characterized via protein marker, transmission electron microscopy, and nanoparticle tracking analysis, then applied in cellular models and mouse models of cardiac fibrosis. Western blotting and qRT-PCR were used to identify protective signaling pathways in cardiac fibroblasts (CFs).

Results: Young-sEVs significantly inhibited cardiac fibrosis and subsequent cardiac dysfunction post-myocardial infarction (MI) in mice. The main findings included that echocardiographic assessments four weeks post-MI indicated that Young-sEVs improved left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), and reduced left ventricular internal diameter in diastole (LVIDd) and systole (LVIDs). Treatment with Young-sEVs also decreased Masson-positive fibroblast areas and collagen synthesis in cardiac tissue. However, sEVs from the old control group did not achieve the above effect. Consistent with in vivo results, Young-sEVs could also inhibit the proliferation, migration, and collagen synthesis of CFs in the TGF-β1-induced cellular fibrosis model. High-throughput microRNA (miRNA) sequencing and qRT-PCR analysis revealed that miR-664a-3p was abundant in Young-sEVs. The high expression of miR-664a-3p significantly inhibited the proliferation, migration, and collagen synthesis of TGF-β1-induced CFs. However, suppressing the expression of miR-664a-3p in Young-sEVs eliminated their therapeutic effect on cardiac fibrosis in mice. Further studies confirmed SMAD4 as a direct downstream target of miR-664a-3p, whose overexpression could reverse the anti-fibrotic effects of miR-664a-3p.

Conclusion: In summary, these findings firstly revealed that Young-sEVs could directly bind to the 3'-untranslated region of SMAD4 mRNA through miR-664a-3p, thereby inhibiting the TGF-β/SMAD4 signaling pathway to protect heart from fibrosis and improve cardiac function. Considering the ease of obtaining plasma-derived sEVs, our study offers a promising therapeutic strategy for heart failure, with the potential for rapid clinical translation in the near future.

Nanotechnology has emerged as a revolutionary domain with diverse applications in medicine, and one of the noteworthy developments is the exploration of bacterial magnetosomes acquired from magnetotactic bacteria (MTB) for therapeutic purposes. The demand for natural nanomaterials in the biomedical field is continuously increasing due to their biocompatibility and eco-friendly nature. MTB produces uniform, well-ordered magnetic nanoparticles inside the magnetosomes, drawing attention due to their unique and remarkable features. MTB and magnetosomes have gained popularity in cancer treatment and diagnosis, especially in magnetic resonance imaging. Distinctive features highlighted include advancements in extraction, characterization, and functionalization techniques, alongside breakthroughs in utilizing MTB-based magnetosomes as contrast agents in imaging, biocompatible drug carriers, and tools for minimally invasive therapies. The biocompatible nature, functionalizing of the surface of bacterial magnetosomes, and response to the external magnetic field make them a potential candidate for the theragnostic purpose of MTB and magnetosomes. In the present review, emphasis has been given to the foundation of magnetosomes at a genetic level, mass production of magnetosomes, etc. Further authors have reviewed the various functionalization methods of the magnetosomes for cancer treatment. Finally, the authors have reviewed the recent advancements in MTB and magnetosome-based cancer detection, diagnosis, and treatment. Challenges such as scalability, long-term safety, and clinical translation are also discussed, presenting a roadmap for future research exploiting MTBs and magnetosomes' unique properties.

Cancer-associated fibroblasts (CAFs) are a heterogeneous population of non-malignant cells that play a crucial role in the tumor microenvironment, increasingly recognized as key contributors to cancer progression, metastasis, and treatment resistance. So, targeting CAFs has always been considered an important part of cancer immunotherapy. However, targeting CAFs to improve the efficacy of tumor therapy is currently a major challenge. Nanomaterials show their unique advantages in the whole process. At present, nanomaterials have achieved significant accomplishments in medical applications, particularly in the field of cancer-targeted therapy, showing enormous potential. It has been confirmed that nanomaterials can not only directly target CAFs, but also interact with the tumor microenvironment (TME) and immune cells to affect tumorigenesis. As for the cancer treatment, nanomaterials could enhance the therapeutic effect in many ways. Therefore, in this review, we first summarized the current understanding of the complex interactions between CAFs and TME, immune cells, and tumor cells. Next, we discussed common nanomaterials in modern medicine and their respective impacts on the TME, CAFs, and interactions with tumors. Finally, we focus on the application of nano drug delivery system targeting CAFs in cancer therapy.

Purpose: The solid lipid nanoparticles of transitional metal complexes (POMs) were prepared with natural lipids with the aim of developing a safer therapeutic approach for cancer treatment.

Methods: Natural lipids were used to create solid lipid nanoparticles containing transitional metal complexes (POMs).

Results: The nanoparticles had displayed appreciable entrapment and loading percentage of P₅W₃₀. The zeta capacitance was measured to be -32.57±6.44 mV with average particle dimension of 160.5±8.61 nm and polydispersity index (PDI) of around 0.3814±0.096. The effectiveness of P₅W₃₀-BW-SLNs in inhibiting the growth of HeLa cells was found to be higher (IC₅₀ = 3.02±2.14 µg/mL) compared to pure P₅W₃₀ (IC₅₀ = 7.93±5.08 µg/mL). Further examinations of DNA damage were made through comet test and flow cytometry techniques. The assessment of tumor regression and survival was conducted, and comparison was recorded. The P₅W₃₀-BW-SLNs resulted in a 72.91% increase in survival rates and a reduction in tumor burden by 2.967±0.543%. Moreover, the computational findings demonstrate a strong connection with the actual data, providing a plausible explanation for the notable chemopreventive efficacy of POM against HeLa cell lines.

Conclusion: The study's findings might pave the way for a more efficient delivery system in cancer treatment.

Photodynamic therapy (PDT) is a promising noninvasive tumor treatment modality that relies on generating reactive oxygen species (ROS) and requires an adequate oxygen supply to the target tissue. However, hypoxia is a common feature of solid tumors and profoundly restricts the anti-tumor efficacy of PDT. In recent years, scholars have focused on exploring nanomaterial-based strategies for oxygen supplementation and integrating non-oxygen-consuming treatment approaches to overcome the hypoxic limitations of PDT. Some scholars have harnessed the photosynthetic oxygen production of cyanobacteria under light irradiation to overcome tumor hypoxia and engineered them as carriers of photosensitizers instead of inorganic nanomaterials, resulting in photosynthetic bacteria (PSB) attracting significant attention. Recent studies have shown that light-triggered PSB can exhibit additional properties, such as photosynthetic hydrogen production, ROS generation, and photothermal conversion, facilitating their use as promising light-responsive biomaterials for enhancing the anti-tumor efficacy of PDT. Therefore, understanding PSB can provide new insights and ideas for future research. This review mainly introduces the characteristics of PSB and recent research on light-triggered PSB in anti-tumor PDT to enrich our knowledge in this area. Finally, the challenges and prospects of using PSB to enhance the anti-tumor efficacy of PDT were also discussed.