Search Results (973)

Theranostic nanoparticles, which integrate diagnostic imaging and therapeutic delivery within a single nanoplatform, represent a transformative paradigm in oncological nanomedicine. Despite substantial preclinical progress, the field faces persistent gaps in rational nanoparticle design informed by tumor biology, preclinical model fidelity, and clinical translation. This review critically synthesizes theranostic nanoparticle research across three underexplored domains. First, we examine tumor microenvironment features—reactive oxygen species dynamics, glutathione gradients, hypoxia, and proteasomal dysregulation—as mechanistic drivers of nanoparticle responsiveness. Second, we evaluate redox-responsive and proteasome-targeted nanoplatforms that exploit these cues for stimuli-triggered drug release and simultaneous imaging readout. Third, we address the unmet need for three-dimensional organoid and microfluidic tumor models as predictive preclinical testing environments, given the well-documented limitations of conventional two-dimensional cultures. Cancer subtype-specific applications are discussed for breast cancer, HPV-associated malignancies, colorectal cancer, and prostate cancer. Clinical translation barriers—including pharmacokinetic constraints, protein corona formation, immune clearance, anti-PEG antibodies, complement activation-related pseudoallergy, and FDA/EMA regulatory pathways—are addressed from a clinical oncology perspective. The review concludes with a research roadmap integrating proteomics-guided nanoparticle engineering, patient-derived organoid biobanks, and artificial intelligence-assisted design as priority areas for next-generation oncological theranostics. Full article

Nanomedicine-based liposomal delivery systems are gaining increasing attention as advanced therapeutic platforms for managing ocular infections associated with antimicrobial resistance (AMR) and biofilm formation. The primary objective of this review is to critically evaluate the potential of liposomal drug delivery systems for improving the treatment of antimicrobial-resistant and biofilm-associated ocular infections by integrating current knowledge on antimicrobial resistance mechanisms, biofilm-targeted therapeutic strategies, and advances in liposomal formulations, while also identifying the major limitations, translational challenges, and knowledge gaps in this rapidly evolving field. Traditional ocular antimicrobial treatments are frequently limited by poor drug penetration, short precorneal residence time, low bioavailability, systemic side effects, and inadequate activity against resistant microorganisms and biofilm-embedded pathogens. This review provides a comprehensive overview of different liposomal systems, including conventional, cationic, polyethylene glycol (PEG)-modified, deformable, and stimulus-responsive liposomes, and discusses their advantages in ophthalmic drug delivery, such as enhanced corneal permeation, prolonged drug retention, controlled release, improved biocompatibility, and reduced ocular toxicity. The review further examines the mechanisms through which liposomes help overcome AMR, including improved epithelial transport, membrane disruption, intracellular drug delivery, efflux pump evasion, and enhanced antimicrobial efficacy. In addition, liposomal approaches targeting ocular biofilms are explored, focusing on improved biofilm penetration and the delivery of anti-biofilm agents such as antibiotics, enzymes, quorum-sensing inhibitors, and antimicrobial peptides. Current evidence from in vitro and in vivo ocular infection models is summarized together with disease-specific applications in keratitis, endophthalmitis, and contact lens-related infections. The article also compares liposomes with other ocular nanocarriers and addresses important considerations related to safety, stability, sterilization, large-scale production, and regulatory translation. In addition to highlighting recent advances, this review critically discusses the current limitations of liposomal formulations, the major barriers to clinical translation, and the key knowledge gaps that should be addressed to facilitate the future development and successful clinical application of these systems. Finally, emerging directions including ligand-targeted and stimulus-responsive liposomes, AI-driven formulation development, personalized nanotherapy, and gene therapy combinations are discussed as promising future strategies for combating resistant ocular infections. Full article

The growing global crisis of antimicrobial resistance (AMR) urgently demands non-classical therapies capable of evading established resistance mechanisms. Bacterial ferroptosis-like death, an iron-dependent process driven by lipid peroxidation, offers a promising strategy to circumvent conventional drug resistance. However, the clinical translation of ferroptosis-like inducers is hindered by poor water solubility and off-target systemic toxicity. Featuring tunable physicochemical characteristics and proven clinical biosafety, liposomes stand out as a viable platform to resolve these translational bottlenecks. Although antibacterial nanomedicines have been extensively investigated, the specific synergies between liposomal engineering and bacterial ferroptosis-like pathways remain underexplored. To bridge this gap, this review systematically delineates the molecular cascades of bacterial ferroptosis-like death and highlights unique mechanistic advantages of liposomes. Importantly, liposome-mediated ferroptosis-like antibacterial therapy faces prominent translational challenges, including biosafety concerns, insufficient stability, and targeting limitations. This review further outlines advanced liposomal engineering strategies to tackle the above obstacles and discusses pressing questions that should be the focus of future ferroptosis-like research. By integrating multidisciplinary research outcomes, this review may provide insights and feasible design guidelines to advance the translational development of liposomal ferroptosis-like inducers against AMR infections. Full article

Since the introduction of the spherical nucleic acid (SNA) paradigm in 1996, extensive research has been dedicated to this burgeoning field, yielding groundbreaking advances in biomedicine. Featuring a unique three-dimensional spherical nanoarchitecture composed of highly oriented, densely packed oligonucleotide layers conjugated to a solid or hollow core, SNAs possess extraordinary biological properties, including transfection-reagent-independent cellular internalization and enhanced resistance to nuclease degradation. These synthetic and foundational evolutionary milestones offer profound advantages for the rational design of targeted biomedical therapeutics. In this comprehensive review, recent breakthroughs in the synthetic methodologies and structural designs of SNAs, with a particular emphasis on gold-based templates, are systematically summarized and discussed. Furthermore, the core bottlenecks and future perspectives emerging at the intersection of artificial intelligence and high-throughput screening are highlighted to guide next-generation intelligent nanomedicine development. Full article

Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer nanostructures containing endogenous lipids, proteins, nucleic acids, and phytochemicals, which have attracted increasing interest as bioinspired carriers for cancer therapy. This review evaluates how plant source, isolation, purification procedures, vesicle composition, cargo-loading strategy, and administration route shape the quality and tumor-delivery performance of PELNs. The available evidence indicates that plant source and processing are major determinants of particle size, purity, surface charge, cargo profile, and biological activity. Ultracentrifugation remains widely used but is limited by contaminant co-isolation and poor scalability, whereas density-gradient purification and size-exclusion chromatography improve purity, and ultrafiltration and tangential flow filtration offer greater potential for large-scale manufacturing. Passive incubation generally preserves vesicle integrity and is most suitable for hydrophobic small molecules, whereas electroporation, sonication, and extrusion can increase cargo loading but may cause aggregation, membrane remodeling, or loss of endogenous components. Preclinical studies suggest that PELNs can exert intrinsic antitumor effects, modulate the tumor microenvironment, improve chemotherapeutic delivery, and help overcome drug resistance. However, evidence for in vivo tumor-targeting remains less robust than evidence for cellular uptake, and direct comparisons with established nanocarriers remain scarce. Clinical translation will require standardized nomenclature and characterization, reproducible manufacturing, quantitative loading and release assays, route-specific biodistribution studies, and repeated-dose safety evaluation. These findings provide a framework for the rational development of PELNs as reproducible tumor-oriented nanocarriers. Full article

Myocarditis is a clinically challenging form of inflammatory heart disease with heterogeneous etiologies, limited diagnostic tools, no targeted therapies, and a substantial risk of progression to heart failure or sudden cardiac death, particularly in young adults. Emerging evidence has increasingly associated myocarditis with gut microbiota dysbiosis. This review explores the gut–myocarditis axis, highlighting key mechanisms and therapeutic strategies. Significant alterations in gut microbial composition are observed in myocarditis patients and animal models. Gut microbiota influences disease development through multiple pathways: compromised intestinal barrier integrity leading to bacterial translocation and systemic inflammation via MAMP/PRR signaling (e.g., TLRs, NLRs); production of metabolites—including pro-inflammatory trimethylamine N-oxide (TMAO), anti-inflammatory short-chain fatty acids (SCFAs), and immunomodulatory bile acids—that regulate host inflammatory responses, immune cell differentiation, oxidative stress, and fibrotic remodeling; and molecular mimicry, where microbial peptides (e.g., from Bacteroides thetaiotaomicron) trigger cross-reactive autoimmune responses against cardiac proteins. Regarding therapeutic strategies, this review discusses fecal microbiota transplantation (FMT), probiotics, prebiotics, dietary modulation, and emerging approaches including engineered bacteria and oral nanomedicines. Although these strategies hold promise, their efficacy and safety remain to be validated in large-scale clinical trials, and further investigation is warranted. Full article

Inhalable ribonucleic acid (RNA) nanomedicines are emerging as versatile therapeutics for respiratory diseases and pulmonary metastases, enabling localized delivery of messenger RNA (mRNA), small interfering RNA (siRNA), antisense oligonucleotides, microRNA (miRNA) mimics, self-amplifying RNA, and genome-editing systems. This review synthesizes the available evidence and argues that the field has moved beyond asking whether RNA can reach the lungs. The more consequential translational question is whether RNA cargo, nanocarrier, excipients, manufacturing process, inhalation device, and pulmonary target cell can be integrated into a reproducible therapeutic product. Current research demonstrates progress in disease-corrective mRNA expression, silencing of inflammatory and fibrotic pathways, mucosal vaccination, antiviral therapy, and localized cancer treatment, alongside advances in ionizable lipid nanoparticles, lipid–polymer hybrids, chitosan and polyethyleneimine (PEI) polyplexes, dendrimers, peptide carriers, biomimetic systems, and dry-powder formulations. Translational maturity, however, remains uneven. Many studies demonstrate carrier feasibility, reporter expression, or preclinical activity, whereas fewer establish device-compatible aerosolization, preservation of RNA integrity during processing, traversal of pulmonary barriers, target-cell engagement, repeat-dose tolerability, and clinically meaningful benefit. Development should therefore be target-defined, analytically gated, device-specific, and outcome-centered. Inhalable RNA nanomedicines are best understood as integrated pulmonary products whose success depends on preserving RNA function throughout manufacturing, aerosolization, post-deposition barrier navigation, intracellular delivery, and disease-relevant pharmacodynamic activity. Full article

While anti-tumor drugs markedly improve patient survival, dose-limiting toxicities remain major constraints on clinical efficacy and quality of life. Conventional management strategies lack timeliness and precision. Traditional Chinese medicine (TCM) and its active ingredients offer unique potential for mitigating anti-tumor drug toxicities through multi-component and multi-target regulation. However, the transformation of TCM is hampered by poor bioavailability and targeting. This review summarizes and evaluates an integrated strategy combining TCM with nanotechnology to develop novel nanomedicines. It elucidates the distinct toxicity mechanisms of chemotherapy drugs, targeted drugs, and immunotherapy drugs, revealing toxicopathological transitions from non-specific killing to microenvironment disruption and immune imbalance. Subsequently, it discusses the intervention mechanisms and research progress of TCM and its active ingredients targeting different categories of anti-tumor drug toxicity. To overcome delivery challenges, this review explores construction strategies for diverse nanodelivery systems, including carrier-free self-assembled nanomedicines, physically loaded nanomedicines, and chemically coupled nanomedicines, highlighting their value in organ-specific accumulation and controlled release. Finally, it objectively analyzes challenges in the clinical translation of these nanomedicines, encompassing safety and industrialization, while prospecting future trends, aiming to contribute to a new therapeutic paradigm focused on “toxicity attenuation and efficacy potentiation” and steer cancer treatment toward greater precision and intelligence. Full article

Graphene oxide (GO)-based nanomaterials functionalized with targeting ligands are promising platforms for selective cancer drug delivery. Among relevant targets, integrin α_Vβ₃ is a highly overexpressed receptor in several solid tumors and is commonly targeted using cyclic Arg-Gly-Asp (cRGD) peptides. However, the molecular details governing the interaction between cRGD-functionalized GO dots and integrins remain poorly understood. In this work, all-atom molecular dynamics simulations are employed to investigate the interaction between integrin α_Vβ₃ and a nanocarrier composed of a GO dot coated with polyethylene glycol (PEG) and functionalized with cRGD ligands. Multiple 1 μs simulation replicas are used to characterize both specific ligand recognition and non-specific nanocarrier/receptor interactions. The simulations show that cRGD binding within the integrin-binding pocket is stable, indicating that the nanocarrier does not impair receptor recognition. Beyond cRGD-mediated binding, both PEG-cRGD chains and GO itself establish additional contacts with the protein, whose nature and distribution are modulated by the relative orientation of the GO plane. Overall, the structural dynamics of integrin α_Vβ₃ remains preserved upon nanocarrier binding. These findings provide atomistic insights into the interplay between ligand-mediated and multivalent surface-mediated interactions of GO-based nanocarriers with integrins for the rational design of selective nanocarriers for cancer therapy. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is undergoing a profound epidemiological shift from viral etiologies toward metabolic dysfunction-associated steatohepatitis (MASH). Current targeted therapies often fail to provide effective responses due to the complex, interconnected nature of the tumor microenvironment. This review aims to explain the molecular axis linking chronic metabolic injury to carcinogenesis, focusing specifically on the oncoproteins Astrocyte elevated gene-1/metadherin (AEG-1/MTDH) and staphylococcal nuclease and tudor domain-containing 1 (SND1) as cooperating regulators of this disease network. Methods: This article represents a narrative review of the published literature and does not follow a systematic or exhaustive search protocol. A structured literature search using specific search terms was conducted across PubMed, Scopus, and Web of Science databases, with a last search date of May 2026. Results: Available preclinical data indicate that AEG-1 mediates early preneoplastic injury via dysregulation of hepatic lipid metabolism leading to lipotoxicity and survival of genetically unstable hepatocytes. As the disease progresses, AEG-1 amplifies NF-κB-driven inflammation and, as tumors emerge, recruits SND1 as a cooperating partner to form a gene-silencing complex that suppresses tumor suppressor proteins. Furthermore, AEG-1 and SND1 reprogram surrounding macrophages into an immunosuppressive state and drive tumor resistance to standard anti-angiogenic and chemotherapeutic drugs. Conclusions: The evidence reviewed supports a model in which HCC is driven by an interconnected metabolic-inflammatory-oncogenic cycle. AEG-1 functions as an upstream metabolic and inflammatory driver that cooperates with SND1 in a subset of oncogenic silencing events within this pathogenic network. Therefore, utilizing advanced nanomedicine platforms to simultaneously target these proteins represents a mechanistically rational therapeutic strategy that warrants further preclinical evaluation in advanced HCC. Full article

Photodynamic therapy (PDT) is a cornerstone non-invasive modality for keratinocytic precancers and non-melanoma skin cancer (NMSC), leveraging selective photosensitizer accumulation, light activation, and reactive oxygen species (ROS) generation. This narrative review synthesized literature from major databases (2010–2025) to comprehensively evaluate PDT’s molecular mechanisms, innovative optimization protocols, and clinical efficacy across actinic keratosis (AK), field cancerization, Bowen’s disease (BD), basal cell carcinoma (BCC), and invasive squamous cell carcinoma (cSCC). The evidence highlights frontline clinical maturity and excellent cosmetic outcomes for superficial lesions (AK, field cancerization, superficial BCC, and BD), with daylight PDT offering a virtually painless alternative for widespread dysplasia. However, therapeutic reliability decreases in thick nodular, pigmented, or high-risk lesions due to optical barriers and tissue hypoxia. To overcome these limitations, advanced physical and chemical enhancements—such as ablative fractional lasers, iron chelators, epigenetically enhanced PDT (ePDT), and targeted nanocarriers—are actively reshaping drug delivery and cellular susceptibility. Furthermore, cyclic PDT serves as an indispensable tissue-sparing intervention for organ transplant recipients and Gorlin syndrome patients. In conclusion, while PDT is highly effective for superficial neoplasias, precise histopathological stratification and the integration of nanomedicine are critical to overcoming current biological barriers in aggressive dermatological malignancies. Full article

Boron neutron capture therapy (BNCT) is a radiotherapeutic modality that enables tumor-targeted cell killing. The nuclear capture reaction between boron-10 (¹⁰B) and low-energy thermal neutrons produces high linear energy transfer (LET) particles (α-particles and recoiling lithium nuclei), each of which have short path lengths within the diameter of a single mammalian cell. The deposited energy creates clustered DNA double-strand breaks that are cytotoxic in these tumor cells while sparing the surrounding healthy tissues. This advantage makes BNCT a highly attractive treatment modality compared to conventional radiotherapy. Nevertheless, despite its theoretical precision, the clinical translation of BNCT remains constrained by suboptimal tumor-selective boron delivery; insufficient intracellular accumulation; and heterogeneous biodistribution profiles associated with conventional small-molecule-based boron agents, such as boronophenylalanine (BPA) and sodium borocaptate (BSH). While the development of new accelerator-based neutron sources (ABNSs) has renewed interest in BNCT, effective ¹⁰B delivery remains a major challenge. To address this, nanomedicine has been steadily on the rise in cancer research. In recent years, nanocarrier-based delivery systems have emerged as a transformative alternative delivery strategy. Nanodrugs offer several advantages over conventional small-molecule drugs, such as improved solubility, increased plasma half-life, enhanced permeability and retention in tumors, and active targeting, as well as decreased systemic toxicity and drug resistance. In recent years, nanocarrier-based delivery systems have emerged as a transformative strategy for ¹⁰B delivery. In this focused review, we will discuss various types of nanocarriers used for boron drug delivery that enhance boron loading efficiency and evaluate what enables their selective delivery to and accumulation within tumor cells. Full article

Pulmonary drug delivery has become a vital route for both local and systemic treatments because of the unique structure and function of the respiratory system. Unlike oral and injectable dosage forms, inhalation offers a non-invasive, direct route to deliver medicines to the lungs, bypassing gastric degradation and first-pass hepatic metabolism. Common forms such as aerosols, solutions, suspensions, and dry powders are frequently used to treat respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). However, their effectiveness is often limited by physiological and biopharmaceutical barriers, such as mucociliary clearance, enzymatic degradation, and nonspecific deposition, which reduce drug retention and bioavailability. These issues are especially critical for poorly soluble or sensitive molecules, leading to lower drug concentrations at the target site and necessitating frequent dosing. To address these challenges, advanced nanoparticle-based delivery systems are being developed to improve drug stability, targeting, and controlled release within the lungs. At the same time, computational methods, including deposition modeling, physiologically based pharmacokinetic (PBPK) simulations, and AI-driven optimization, are increasingly used in formulation development to predict in vivo performance and boost translational success. This review covers the physiological and biological barriers to pulmonary drug delivery, explores major inhalation routes and dosage forms, and discusses new therapeutic strategies and nanoparticle platforms. It also highlights the growing role of in silico modeling and AI in accelerating the design and optimization of pulmonary treatments, while addressing current challenges, limitations, and regulatory issues in translating pulmonary nanomedicine into clinical practice. Full article

Wet age-related macular degeneration (wAMD) is characterized by choroidal neovascularization (CNV) and remains a major cause of severe vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the current standard of care for wAMD. However, repeated injections are associated with poor adherence, procedure-related complications, and a substantial cumulative treatment burden. Topical nanocarrier-based systems have therefore attracted increasing attention as needle-free approaches for improving posterior segment drug exposure. Complementing broader reviews of ocular nanomedicine, this review specifically examines topical nanocarrier-mediated posterior segment delivery for wAMD, with a focus on three representative platforms: liposomes, polymeric nanoparticles, and polymeric micelles. These systems are engineered through the optimization of particle size, surface properties, drug-loading strategies, and functional modifications to improve payload stability, ocular surface residence, tissue penetration, and lesion-relevant delivery. By integrating formulation design, ocular barrier transport, ocular posterior segment bioavailability, and translational feasibility in the context of wAMD, this review provides a disease-focused and application-oriented perspective that complements existing broader reviews of ocular nanocarriers and ophthalmic nanomedicine. We summarize current evidence from preclinical and translational studies and discuss major barriers limiting clinical application, including insufficient posterior segment drug exposure, dose–safety trade-offs, pharmacokinetic instability, limited targeting efficiency, and challenges in delivering macromolecular biologics, such as anti-VEGF antibodies and fusion proteins. At present, topical nanocarrier-based strategies remain investigational, but they hold potential for development as therapeutic approaches for wAMD. Key priorities for future development include quantitative posterior segment pharmacokinetic/pharmacodynamic evaluation, long-term safety assessment, payload-specific carrier design, scalable manufacturing, and clinically relevant efficacy endpoints. This review provides a focused framework for the rational design and translational assessment of nanocarrier-based topical strategies for wAMD management. Full article

The integration of artificial intelligence (AI) and machine learning (ML) is fundamentally transforming pharmaceutical sciences, shifting drug formulation and nanocarrier design from traditional empirical approaches toward predictive, data-driven methodologies. By enabling the analysis of large, complex datasets, AI technologies are accelerating decision-making, improving formulation efficiency, and supporting the development of more effective therapeutic systems. Despite these advances, the successful clinical translation of advanced nanomedicines, including polymeric nanoparticles and mRNA–lipid nanoparticle platforms, remains limited by challenges such as biological barriers, highly sensitive formulation parameters, scalability issues, and the limited interpretability of many computational models. This review provides a comprehensive overview of AI applications throughout the pharmaceutical development lifecycle. It explores how classical machine learning algorithms and deep learning architectures optimize conventional dosage forms, enhance formulation development, and enable the rational design of targeted nanocarriers. Particular emphasis is placed on predicting critical quality attributes, encapsulation efficiency, physicochemical properties, drug-release behavior, therapeutic efficacy, and early-stage nanotoxicity. Furthermore, we critically assess the regulatory considerations, manufacturing constraints, data quality issues, and tumor microenvironment heterogeneity that continue to impede bench-to-clinic translation. Ultimately, overcoming these challenges requires moving beyond isolated algorithmic optimization toward an integrated framework that combines computational intelligence, robust experimental validation, and continuous clinical feedback. Such a synergistic approach is expected to drive the next generation of precision nanomedicine and facilitate the safe and effective translation of AI-enabled pharmaceutical innovations into clinical practice. Full article