International Journal of Nanomedicine最新文献

Background: Natural photosensitizers hold potential for photodynamic therapy (PDT) but are often limited by poor visible light absorption. Plant-derived exosome-like nanovesicles offer an innovative platform for enhancing photosensitizer performance.

Methods: Hypericum perforatum-derived nanovesicles (HPDENs) were characterized using electron microscopy, dynamic light scattering, and proteomic and miRNA sequencing. High-performance liquid chromatography confirmed hypericin content. PDT efficacy was assessed in vitro and in vivo.

Results: HPDENs exhibited robust photosensitizing properties, generating reactive oxygen species (ROS) through both Type I and Type II pathways upon light activation. In vitro, HPDENs showed light dose-dependent cytotoxicity against human melanoma cells, characterized by elevated ROS production and apoptosis induction. In vivo, HPDEN-mediated PDT significantly suppressed tumor growth and induced extensive tumor necrosis, with no observable toxicity to major organs.

Conclusion: HPDENs represent a novel plant-derived photosensitizer with dual ROS generation pathways and significant therapeutic efficacy, providing a promising platform for enhancing photodynamic therapy.

Macrophage immunotherapy is an emerging therapeutic approach designed for modulating the immune response to alleviate disease symptoms. The balance between pro-inflammatory and anti-inflammatory macrophages plays a pivotal role in the progression of inflammatory diseases. Mitochondria, often referred to as the "power plants" of the cell, are essential organelles responsible for critical functions such as energy metabolism, material synthesis, and signal transduction. The functional state of mitochondria is closely linked to macrophage polarization, prompting interest in therapeutic strategies that target mitochondria to regulate this process. To this end, biomaterials with excellent targeting capabilities and effective therapeutic properties have been developed to influence mitochondrial function and regulate macrophage polarization. However, a comprehensive summary of biomaterial-driven modulation of mitochondrial function to control macrophage phenotypes is still lacking. This review highlights the critical role of mitochondrial function in macrophage polarization and discusses therapeutic strategies mediated by biomaterials, including mitochondria-targeted biomaterials. Finally, the prospects and challenges of the use of these biomaterials in disease modulation have been explored, emphasizing their potential to be translated to the clinic. It is anticipated that this review will serve as a valuable resource for materials scientists and clinicians in the development of next-generation mitochondria-targeted biomaterials.

Tissue injury repair is a multifaceted and dynamic process characterized by complex interactions among various immune cells, with M2 macrophages assuming a crucial role. Exosomes derived from M2-type macrophages (M2-Exos) significantly influence the injury repair process through intercellular communication mediated by enriched microRNAs (miRNAs). This review aims to elucidate the biological processes underlying exosome formation, the synthesis and function of miRNAs, and the diverse methodologies employed for exosome extraction. Furthermore, we provide a comprehensive summary of the established multifarious functions and mechanisms of M2-Exos miRNAs in tissue injury repair across different systems, while also exploring their potential applications in disease prevention, diagnosis, and clinical practice. Despite the challenges encountered, the therapeutic use of M2-Exos in clinical contexts appears promising, prompting research efforts to focus on improving the efficiency of exosome extraction and application, as well as ensuring the safety of their clinical utilization.

Given the complexity of the central nervous system (CNS) and the diversity of neurological conditions, the increasing prevalence of neurological disorders poses a significant challenge to modern medicine. These disorders, ranging from neurodegenerative diseases to psychiatric conditions, not only impact individuals but also place a substantial burden on healthcare systems and society. A major obstacle in treating these conditions is the blood-brain barrier (BBB), which restricts the passage of therapeutic agents to the brain. Nanotechnology, particularly the use of nanoparticles (NPs), offers a promising solution to this challenge. NPs possess unique properties such as small size, large surface area, and modifiable surface characteristics, enabling them to cross the BBB and deliver drugs directly to the affected brain regions. This review focuses on the application of NPs in gene therapy and enzyme replacement therapy (ERT) for neurological disorders. Gene therapy involves altering or manipulating gene expression and can be enhanced by NPs designed to carry various genetic materials. Similarly, NPs can improve the efficacy of ERT for lysosomal storage disorders (LSDs) by facilitating enzyme delivery to the brain, overcoming issues like immunogenicity and instability. Taken together, this review explores the potential of NPs in revolutionizing treatment options for neurological disorders, highlighting their advantages and the future directions in this rapidly evolving field.

Background and aim: Over the past years, noble metal-based nanoparticles have been extensively investigated for their applications in nanomedicine. However, there are still concerns about the potential adversities that these nanoparticles may present in an organism. In particular, whether they could cause an exacerbated cytotoxic response in susceptible tissues due to damage or disease, such as the heart, liver, spleen, or kidneys. In this regard, this study aims to evaluate the cytotoxicity of mono- and bimetallic nanoparticles of gold and silver (Au:Ag NPs) on healthy and hypertrophic cardiac H9c2 cells, and on healthy and metabolically activated macrophages derived from U937 cells. The main objective of this work is to explore the susceptibility of cells due to exposure to Au:Ag NPs in conditions representing cardiometabolic diseases.

Methods: Au:Ag NPs were synthesized in different molar ratios (Au:Ag, 100:0, 75:25, 50:50, 25:75, 0:100) using starch as a capping and reducing agent. Their physicochemical properties were characterized through UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), ζ-potential measurements, and transmission electron microscopy (TEM). Moreover, the effect of the metal-based nanoparticle exposure on healthy and hypertrophic H9c2 cells was measured by analyzing the cellular vitality, the loss of mitochondrial membrane potential (∆Ψm), and the production of mitochondrial reactive oxygen species (mROS).

Results: The Au:Ag NPs did not affect the cell vitality of healthy or metabolically activated macrophages. On the contrary, healthy H9c2 cells showed decreased mitochondrial metabolism when exposed to NPs with higher Ag concentrations. Furthermore, hypertrophic H9c2 cells were more susceptible to the same NPs compared to their non-hypertrophic counterparts, and presented a pronounced loss of ∆Ψm. In addition, these NPs increased the production of mROS and regulated cell death in both cardiac cells.

Conclusion: In conclusion, low doses of high-Ag load in Au:Ag NPs produced cytotoxicity on H9c2 cardiac cells, with hypertrophic cells being more susceptible. These results suggest that cardiac hypertrophic conditions are more prone to a cytotoxic response in the presence of bimetallic Au:Ag NPs compared to healthy cells. In addition, this work opens the door to explore the nanotoxicity of noble metal-based NPs in biological disease conditions.

Kidney stones constitute a common condition impacting the urinary system. In clinical diagnosis and management, traditional surgical interventions and pharmacological treatments are primarily utilized; however, these methods possess inherent limitations. Presently, the field of nanomedicine is undergoing significant advancements. The application of nanomaterials in biosensors enables the accurate assessment of urinary ion composition. Furthermore, contrast agents developed from these materials can improve the signal-to-noise ratio and enhance image clarity. By mitigating oxidative stress-induced cellular damage, nanomaterials can inhibit the formation of kidney stones and enhance the efficacy of drug delivery as effective carriers. Additionally, by modifying the physical and chemical properties of bacteria, nanomaterials can effectively eliminate bacterial presence, thereby preventing severe complications. This review explores the advancements in nanomaterials technology related to the early detection of risk factors, clinical diagnosis, and treatment of kidney stones and their associated complications.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, primarily arises from defects in the colonic barrier, imbalances of the gut microbiota, and immune response issues. These complex causes make it difficult to achieve a complete cure. Patients with IBD frequently experience recurrent abdominal pain and bloody diarrhea, while severe cases may result in intestinal obstruction, perforation, and cancer. Lifelong maintenance therapy may thus be needed to manage these symptoms; however, traditional IBD drugs, such as 5-aminosalicylic acid, glucocorticoids, immunosuppressants, and biological agents, are often associated with problems including poor solubility, instability, and ineffective targeting, as well as causing serious side effects in non-target tissues. Nanomaterial drug delivery systems (NDDS) have recently shown great promise in optimizing drug distribution, solubility through biocompatible coatings, enhancing bioavailability via PEGylation and reducing side effects. These formulations can enhance a drug's pharmacokinetics by modifying its properties, improve its ability to cross barriers, and boost bioavailability. In addition, NDDS can enable targeted delivery, increase local drug concentrations, improve efficacy, and reduce side effects, as well as protecting active drug molecules from immune recognition and protease degradation. The clinical use of these systems for treating IBD, however, requires further research. This review summarizes the classification of NDDS for IBD, and concludes that, despite ongoing challenges, NDDS may represent an effective treatment approach for IBD. In summary, NDDS enhance the targeted delivery of therapeutic agents to specific cells or tissues, thereby improving drug bioavailability and therapeutic efficacy. These systems effectively surmount biological barriers, facilitating efficient drug delivery to targeted sites, which is crucial for attaining optimal therapeutic outcomes. This review contributes to a deeper understanding of how the physicochemical properties of NDDS influence pharmacological behavior in vivo and can expedite their clinical translation.

Breast cancer is one of the most common types of cancer in women worldwide and is a leading cause of cancer deaths among women. As a result, various treatments have been developed to combat this disease. Breast cancer treatment varies based on its stage and type of pathology. Among the therapeutic options, ultrasound has been employed to assist in the treatment of breast cancer, including radiation therapy, chemotherapy, targeted immunotherapy, hormonal therapy, and, more recently, radiofrequency ablation for early-stage and inoperable patients. One notable advancement is ultrasound-targeted microbubble destruction (UTMD), which is gradually becoming a highly effective and non-invasive anti-tumor modality. This technique can enhance chemical, genetic, immune, and anti-vascular therapies through its physical and biological effects. Specifically, UTMD improves drug transfer efficiency and destroys tumor neovascularization while reducing toxic side effects on the body during tumor treatment. Given these developments, the application of ultrasound-assisted therapy to breast cancer has gained significant attention from research scholars. In this review, we will discuss the development of various therapeutic modalities for breast cancer and, importantly, highlight the application of ultrasound microbubble-targeted disruption techniques in breast cancer treatment.

Background: Silver nanoparticles (AgNPs) have a broad spectrum of biocidal effects, allowing also their antitumor application. To enhance bioavailability, minimize adverse effects and enable targeted drug delivery AgNPs may be encapsulated in liposomes. In this study we aimed to create highly stable and effective antitumor AgNP lipid formulations (LAgs).

Methods: Uncapped and citrate-stabilized AgNPs were encapsulated by the lipid film hydration method using several phospholipid mixtures, followed by the essential removal of unencapsulated AgNPs by size exclusion chromatography (SEC). Purified LAgs were characterized by UV-VIS, DLS, XRD, ICP-MS, transmission electron microscopy (TEM) and glycerol-based density gradient centrifugation (DGC). Liposomal stability was assessed by carboxyfluorescein (CF) leakage, while antitumor effects of purified LAgs were tested in MTT, clonogenic and 3D spheroid invasion experiments.

Results: The presence of AgNPs inside SEC-purified liposomes was confirmed by TEM, XRD and ICP-MS. Encapsulation efficiency was estimated to be between 18.7 and 25.5%. Purified LAgs had higher density as compared to free AgNPs revealed by DGC, indicating that a considerable fraction of liposomes contained AgNPs. LAgs with PC/PG, PC/PG/SM/Chol, and in particular PC/PG/SM displayed the highest stability assessed by CF leakage, whereas high content of neutral or negatively charged phospholipids was destabilizing. As shown by MTT and colony formation assays, viability and survival of A375 and RPMI-7951 melanoma cells were severely impaired by LAgs at a higher or comparable level as caused by free AgNPs. Used as a non-tumor control, HEK293 cells were less vulnerable to LAgs as compared to free AgNPs. Finally, applying the most stable lipid composition, PC/PG/SM-LAg-c, and in part PC/PG/SM-LAg-u effectively inhibited a tissue-like invasion of melanoma spheroids.

Conclusion: Altogether, highly stable purified LAg formulations were created, which effectively block survival, clonogenic potential and invasion of melanoma cells, therefore could be promising NP platforms for targeted tumor therapy.