International Journal of Nanomedicine最新文献

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with brain metastases occurring in 24% to 40% of advanced NSCLC patients and a poor prognosis. Traditional treatment methods for brain metastases, such as surgery and radiotherapy, often result in neurocognitive impairment and brain edema. Furthermore, chemotherapy drugs struggle to penetrate the central nervous system. Third-generation EGFR-TKI drugs that can cross the blood-brain barrier have demonstrated efficacy in treating NSCLC patients with brain metastases, but their benefits are limited to those with specific driver genes. Immunotherapy demonstrated potential in the treatment of NSCLC patients with brain metastases, although the adverse events limited its clinical use. Given these limitations, filamentous phages emerge as a promising bio-nanomaterial due to their unique biosafety profile, high solubility, and ability to facilitate targeted delivery, which can potentially minimize systemic toxicity. This review focuses on two core applications of filamentous phages in NSCLC and brain metastasis therapy: (i) phage display-derived targeting peptides and (ii) intact engineered filamentous phages as delivery scaffolds. As delivery systems, filamentous phages can prolong in vivo circulation time, reduce toxicity, and effectively cross the Blood-Brain Barrier (BBB)-evidences include filamentous phage mediating targeted delivery of chemotherapeutics and siRNA to NSCLC cells, and phage-nanomaterial hybrids enhancing tumor accumulation. The review also elaborates on the clinical translation potential of filamentous phages, including personalized therapy via patient-specific peptide screening, and discusses current limitations. Filamentous phage-based nanocarriers are expected to improve the quality of life of NSCLC patients with brain metastases.

Autoimmune diseases are chronic, debilitating conditions caused by the immune system mistakenly attacking healthy tissues. Conventional treatments mainly involve broad immunosuppression, which is associated with significant side effects, limited specificity, and suboptimal long-term outcomes. For instance, continuing to take corticosteroids can result in a number of serious dose-linked toxicities, such as osteoporosis, hypertension, and a markedly increased susceptibility to infection, whereas methotrexate, even at therapeutic doses, can still cause liver damage and bone marrow suppression. This review aims to explore recent advances in nanotechnology-based therapies for autoimmune diseases, focusing on their mechanisms, therapeutic applications, and potential for clinical translation. A comprehensive review of peer-reviewed literature was conducted to examine various nanotechnology platforms, including drug-loaded nanoparticles, antigen-specific nanomedicines, RNA interference (siRNA), CRISPR-enabled systems, and stimuli-responsive nanocarriers. For instance, methotrexate-loaded polymeric nanoparticles dramatically decreased arthritis severity in preclinical rheumatoid arthritis rodents, whereas PLGA nanoparticles containing gluten protein induced immunological tolerance in a clinical study for celiac disease. Nanomedicine offers several advantages over traditional therapies, including targeted drug delivery, enhanced bioavailability, reduced systemic toxicity, and the potential to induce immune tolerance. Notable innovations include biodegradable polymeric nanoparticles, liposomes, micelles, exosome-mimetic nanoparticles, and magnetic nanomaterials. Emerging technologies, such as CRISPR-Cas9 and RNAi, delivered via nanoparticles, are advancing immune modulation in autoimmune models. Despite promising outcomes, several barriers remain, including concerns about toxicity, scale-up manufacturing issues, and regulatory challenges. Nanotechnology is redefining autoimmune disease therapy by shifting from non-specific immunosuppression to precision-targeted approaches. Future progress lies in integrating nanomedicine with personalized medicine to tailor treatments based on individual immune profiles. Continued interdisciplinary collaboration and regulatory alignment are essential to translating these innovations into clinical practice.

Background: Bladder cancer, particularly non-muscle-invasive bladder cancer (NMIBC), poses significant clinical challenges due to its high recurrence rate. Traditional diagnostic approaches such as cystoscopy and urine cytology have limitations, including invasiveness and insufficient sensitivity. Gold nanoparticles (AuNPs) offer unique opportunities to address these challenges with their surface plasmon resonance effect, biocompatibility, and ease of functionalization.

Methods: Through critical review of recent literature, this paper outlines the application principles, achievements, and mechanisms of AuNPs in bladder cancer, including in vitro diagnostics, multimodal molecular imaging, photothermal therapy, targeted drug delivery, radiotherapy sensitization, and tumor immune microenvironment remodeling.

Main findings: AuNPs are driving a paradigm shift in bladder cancer management. In diagnostics, AuNP-based biosensors enable ultra-sensitive detection of urinary biomarkers. In imaging, they serve as effective contrast agents for enhanced visualization. For therapy, AuNP-mediated photothermal therapy enables precise tumor ablation, and as drug carriers, they help overcome chemoresistance. Additionally, AuNPs demonstrate potential in remodeling the immunosuppressive microenvironment through modulation of signaling pathways and tumor-associated macrophages.

Conclusion: Gold nanoparticles are transforming bladder cancer toward precision, minimally invasive, and personalized treatment models. However, it is important to acknowledge that most current findings remain in the preclinical stage, and significant translational barriers-particularly long-term biosafety and standardized production-must be addressed before widespread clinical adoption.

Introduction: Malignant tumors seriously affect people's normal lives, but the effective treatment of cancer needs to be further improved.

Methods: In this study, we prepared nanocomposites with photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) properties named Fe₂O₃/GCN/ICG/DHA. Under high H₂O₂ conditions, Fe³⁺ is reduced to Fe²⁺ and reacts with DHA to produce C-center free radicals, which kill tumor cells. In addition, ICG produced a warming effect and cytotoxic singlet oxygen with 808 nm laser irradiation.

Results: The significant combined antitumor activity of Fe₂O₃/GCN/ICG/DHA, validated in vitro and in vivo, provides strong experimental support for advancing this transition metal iron-based nanocomplex towards tumor therapy applications.

Discussion: It expands the potential applications of novel nanocomplex in the field of tumor therapy.

Background: Cytosolic protein delivery enables the direct transport of exogenous proteins into the cytoplasm, offering a powerful approach for precise regulation of intracellular activities. This strategy facilitates the investigation of complex physiological processes in cellular and molecular biology and supports the development of protein-based biotechnologies and precision therapeutics, such as targeted protein supplementation for cellular repair or modulation of aberrant cellular functions. However, current delivery methods face some challenges, including cytotoxicity, immune activation, and the difficulty of maintaining protein stability and activity during transport.

Methods: Here, we report a novel AIEgen (Aggregation-induced emission luminogen) -based carrier, MTPABP-Guided-Intracellular-Carrier (MAGIC), that achieves high efficiency in delivering native proteins into the cytosol. MAGIC is capable of binding both negatively and positively charged proteins and mediates their intracellular transport via clathrin-mediated uptake with endosomal escape.

Results: Notably, the β-Gal and HRP proteins delivered by MAGIC maintain their biological activity after delivery, and the cytotoxicity of MAGIC is approximately 40% lower than that of Lipo8000 and TranEX. MAGIC efficiently delivered trypsin, RNase A, and saporin into the cytosol of mammalian cell lines while preserving their enzymatic or functional activity.

Conclusion: This rationally designed AIEgen-based platform provides a versatile and efficient solution for cytosolic protein delivery. The MAGIC delivery system holds significant promise for advancing the study of cellular physiology and enabling precise therapeutic interventions.

The clinical advancement of cancer nanomedicine is significantly hindered by its limited accumulation in tumors, a key factor behind the frequent failure of nanodrugs in clinical trials. The effectiveness of these nanodrugs is closely tied to their route of administration, whether oral, transdermal, intravenous, or intracerebral, as each path presents unique physiological barriers that impede bioavailability and precise tumor targeting. Among the major causes of poor accumulation are rapid clearance by the mononuclear phagocyte system, opsonization accompanied by protein corona formation, renal filtration, and the abnormal, heterogeneous nature of tumor vasculature that restricts passive targeting via the enhanced permeability and retention (EPR) effect. In response, active targeting (AT) strategies have been widely explored, including surface modification with ligands, antibodies, or aptamers designed to bind specifically to overexpressed receptors on cancer cells or blood vessels. Despite these efforts, challenges such as the dense extracellular matrix, elevated interstitial fluid pressure, and the notable inconsistency of the EPR effect between animal models and human patients continue to limit therapeutic penetration. This review offers a systematic examination of nanodrug delivery pathways and the reasons behind their inadequate accumulation, highlighting the potential of both active targeting and combined passive-active strategies to enhance tumor-specific delivery. Overcoming these biological barriers through refined nano-design is crucial for developing the next generation of nanomedicines with improved tumor accumulation and treatment outcomes.

Recent advances in genomics and molecular biology have accelerated the development of nucleic acid-based therapeutics. To optimize their clinical efficacy, various delivery systems-including lipid nanoparticles, polymeric nanomaterials, inorganic nanoparticles (NPs), extracellular vesicles (EVs), viral vectors, protein carriers, and nucleic acid conjugates-have been explored to improve stability, cellular uptake, and bioavailability. This review provides an overview of the current state of nucleic acid therapeutics, focusing on their classification, delivery strategies, and applications in metabolic and inflammatory diseases. Emphasis is placed on the mechanisms of action, targeted delivery approaches, and the existing challenges these systems face. Literature was sourced from PubMed and Web of Science, relevance to the topic, and publication timeline (2020-2025). The aim is to propose insights into the optimization of nucleic acid drugs and the development of novel delivery systems, offering new perspectives for the treatment of complex diseases.

Purpose: In this study, we report the design and evaluation of Anlo@MOF-Lipo (AML), a liposome coated, small sized MIL-101(Fe) metal-organic framework (MOF) for targeted delivery of the multi target tyrosine kinase inhibitor anlotinib in lung cancer treatment.

Methods: In detail, the biomimetic liposome shell enhances nanoparticle biocompatibility, while the MIL-101(Fe) core enables pH responsive release of Fe³⁺ under acidic tumor conditions, triggering Fenton-like reactions and generating cytotoxic reactive oxygen species. Anlotinib is encapsulated within the MOF pores for sustained, intratumoral release, suppressing the growth of tumors.

Results: Characterization confirmed uniform liposome coating and sustained anlotinib release of AML. In vitro, AML demonstrated superior cellular uptake and cytotoxicity in lung cancer cells. In a murine subcutaneous tumor model, AML treatment achieved a greater tumor volume reduction than free anlotinib, with no observable systemic toxicity. Furthermore, in the orthotopic lung cancer model, AML achieved the most pronounced therapeutic efficacy among all treatment groups.

Conclusion: This dual mode therapeutic strategy-combining targeted chemotherapy with oxidative stress induction-highlights the potential of AML as a promising nanomaterial for improving lung cancer treatment.

Preeclampsia (PE), a pregnancy-specific disorder characterized by hypertension and placental dysfunction, remains a leading cause of maternal and fetal morbidities worldwide. Recent advances in nanomedicine offer promising therapeutic strategies by targeting placental pathologies. Studies have demonstrated that in PE mouse models, the regulation of key disease-related genes (such as sFlt1 and VEGF) using siRNA- or mRNA-loaded carriers (eg, lipid nanoparticles, exosomes, or elastin-like polypeptides) can effectively alleviate PE symptoms. This review summarizes the progress in nanoparticle-based therapies for PE, discusses challenges such as scalability and clinical translation, and highlights the potential of nanomedicine to revolutionize PE management.

Introduction: Chemotherapy, the first approach in breast cancer management, is limited owing to systemic toxicity and drug resistance. For instance, 5-fluorouracil in recommended doses cause severe side effects, highlighting the urgent necessity of finding more effective and safer combinations. Hence, this study aims to develop biocompatible natural-based nanocarriers for the co-delivery of loratadine, an antihistaminic drug along with 5-fluorouracil in order to enhance the anticancer efficacy while reducing the required dose of 5-fluorouracil.

Methods: In silico virtual screening was performed to examine the probable molecular interactions between loratadine or 5-fluorouracil, individually with two different polymers, chitosan and zein, to determine the most suitable carrier system. Zein exhibited superior binding affinity compared to chitosan. Nanoparticle optimization was conducted using a Box-Behnken design with zein, tannic acid, and either loratadine or 5-fluorouracil concentration as independent variables. The optimized formulations were characterized by dynamic light scattering, entrapment efficiency, morphology, in-vitro release, followed by cytotoxicity, apoptosis, and cell-cycle analyses in MCF-7 cells.

Results: The optimal formulation consisted of zein (50 mg), tannic acid (131.93 mg), and loratadine or 5-fluorouracil (5 mg). The optimized formulation of Loratadine loaded nanoparticles (NPs) showed a particle size of 197 nm, polydispersity index (PDI) of 0.153, zeta potential of -21.78 mV, and entrapment efficiency of 61.33%. Furthermore, the optimized 5-fluorouracil loaded nanoparticles exhibited a particle size of 231 nm, 0.170 for PDI, zeta potential of -24.01 mV, and EE of 74.91% for entrapment efficiency. The sustained drug release profile exhibited a controlled pattern over 24-48 h. Flow cytometry results showed that the mixed nanoparticles exhibited potent cytotoxicity equivalent to 5-fluorouracil loaded nanoparticles alone despite containing only half the 5-fluorouracil dose, confirming a potential synergistic effect.

Conclusion: These findings confirmed the potential of drug-loaded nanoparticles as promising drug delivery systems for breast cancer management.