Search Results (314)

Subcutaneous mycoses are a heterogeneous group of chronic fungal infections, usually acquired through traumatic inoculation of environmental fungi and particularly severe in immunocompromised and critically ill patients. These infections involve pathogens with marked morphological and physiopathological diversity, resulting in significant diagnostic and therapeutic challenges. Conventional treatment relies on systemic antifungals such as amphotericin B, itraconazole, and other azoles; however, these therapies are often limited by poor tissue penetration, adverse effects, and prolonged treatment regimens, especially in vulnerable patient populations. In this context, nanodrugs have emerged as promising alternatives by improving solubility, stability, bioavailability, and targeted delivery to infection sites. This review conducted a comprehensive literature search in PubMed, SciELO, ScienceDirect, Web of Science, and Scopus, identifying 31 eligible studies that developed and evaluated antifungal nanosystems using in vitro, ex vivo, and/or in vivo models. Quantitative outcomes included minimum inhibitory concentration (MIC), colony-forming units (CFU), inhibition halo diameter, and survival assays. Overall, the evidence indicates that several nanosystems may overcome key pharmacological limitations of conventional antifungals and enhance therapeutic outcomes. Nevertheless, important translational challenges remain, including toxicity, long-term safety, scalability, and regulatory approval, which must be addressed before clinical implementation. Full article

Background: Oral insulin improves compliance and convenience in patients with diabetes who require regular needle injections. However, the clinical application of oral insulin preparations has been limited due to instability and inefficient permeation through the gastrointestinal tract. In this study, a novel cationic polysaccharide nanodrug delivery platform was designed for efficient oral insulin delivery. Methods: The innovative thiolated trimethyl chitosan-grafted β-cyclodextrin (NCT) was synthesized by utilizing N-trimethyl chitosan (TMC) as the polymer backbone. This involved modifying TMC with thiol group-containing N-acetylcysteine and carboxymethyl-β-cyclodextrin that possesses hydrophobic cavities via an amide condensation reaction. Subsequently, this polymer was employed to construct the NCT nanoparticle system using an ionic cross-linking method. The physicochemical properties of the NCT nanoparticles were systematically analyzed, and their therapeutic efficacy was comprehensively evaluated in streptozotocin (STZ)-induced animal models. Results: The NCT nanoparticles demonstrated mucus adhesion, permeability, and pH sensitivity, which facilitated a slow and controlled release within the gastrointestinal microenvironment due to both ionic electrostatic interactions and disulfide bonding interactions. The experiments revealed in vivo that insulin/NCT nanoparticles extended the retention time of insulin in the small intestine. Blood glucose levels decreased to approximately 39% of the initial level at 5 h post-administration while exhibiting smooth hypoglycemic efficacy. Simultaneously, insulin bioavailability increased to 12.58%. Conclusions: The NCT nanoparticles effectively protect insulin from degradation in the gastrointestinal microenvironment while overcoming intestinal barriers, thereby providing a promising approach to oral biomolecule delivery. Full article

With the intensification of global population aging, the co-morbidity rate of periodontitis and osteoporosis has significantly increased. The two are pathologically intertwined, forming a vicious cycle characterized by bone immunoregulatory dysfunction in the periodontal microenvironment, abnormal accumulation of reactive oxygen species (ROS), and disruption of bone homeostasis. Conventional mechanical debridement and anti-infective therapy can reduce the pathogen load, but in some patients, it remains challenging to achieve long-term stable control of inflammation and bone resorption. Furthermore, abnormal bone metabolism in the context of osteoporosis further weakens the osteogenic response during the repair phase, limiting the efficacy of these treatments. Bioinspired cell membrane-coated nanoparticles (CMNPs) have emerged as an innovative technological platform. By mimicking the biointerface properties of source cells—such as red blood cells, platelets, white blood cells, stem cells, and their exosomes—CMNPs enable targeted drug delivery, prolonged circulation within the body, and intelligent responses to pathological microenvironments. This review systematically explores how biomimetic design leverages the advantages of natural biological membranes to address challenges in therapeutic site enrichment and tissue penetration, in vivo circulation stability and effective exposure maintenance, and oxidative stress and immune microenvironment intervention, as well as functional regeneration supported by osteogenesis and angiogenesis. Additionally, we conducted an in-depth analysis of the key challenges encountered in translating preclinical research findings into clinical applications within this field, including issues such as the feasibility of large-scale production, batch-to-batch consistency, and long-term biosafety. This review lays a solid theoretical foundation for advancing the clinical translation of synergistic treatment strategies for periodontitis with osteoporosis and provides a clear research and development pathway. Full article

Neurodegenerative diseases (NDDs), defined by the progressive loss of neurons, present a major challenge to global health. Oxidative stress and lysosomal dysfunction are both key pathogenic factors in NDDs, and they do not operate in isolation; instead, the vicious cycle they form, often mediated through organellar crosstalk, serves as the core driver of the pathological progression of NDDs, collectively worsening disease outcomes. Specifically, excessive reactive oxygen species (ROS) can disrupt lysosomal membrane integrity through lipid peroxidation and inhibit the activity of vacuolar ATPase (V-ATPase), ultimately leading to impaired lysosomal acidification. Meanwhile, lysosomal dysfunction hinders the clearance of damaged mitochondria (the primary endogenous source of ROS), toxic protein aggregates, and free iron ions. This further exacerbates ROS accumulation and accelerates neuronal degeneration. Conventional therapeutic approaches have limited efficacy, primarily due to the challenges in crossing the blood–brain barrier (BBB), insufficient targeting ability, and an inability to effectively intervene in this pathological loop. Nanotherapeutics, leveraging their tunable physicochemical properties and modular functional design, represent a transformative strategy to address these limitations. This review systematically elaborates on the reciprocal interplay between oxidative stress and lysosomal dysfunction in NDDs, with a particular focus on the central role of lysosome-mitochondria axis dysfunction, critically appraises recent advances in nanotechnology-based targeted therapies, and thereby provides a comprehensive theoretical framework to guide the development of novel NDD therapeutics. Full article

Cancer pain seriously damages the quality of life of patients, and its management urgently needs new strategies with both efficacy and safety. This review deeply analyzes the clinical limitations of WHO’s third-order analgesic strategy in cancer pain management, especially emphasizes the unique value of integrated traditional Chinese and Western medicine in synergy and reduction in adverse reactions, and summarizes the network interaction of related drugs through the regulation of multi-target analgesic mechanisms such as inflammatory factors, ion channels, neurotransmitters, and even glial cells and osteoclast activity in the tumor microenvironment. Building on this foundation, the article systematically analyzed the clinical advantages and limitations of drug delivery systems (DDS): oral sustained and controlled drug delivery system, mucosal drug delivery system (MDDS), transdermal drug delivery system (TDDS), and intrathecal targeted drug delivery (ITDD) in the treatment of cancer pain for the first time. The development prospects of new DDS: microneedles, disposable intrathecal drug delivery, and nano-drug delivery system (NDDS) in cancer pain were summarized in detail. Looking ahead, research into the analgesic mechanisms of drugs holds promise for providing a theoretical foundation for cancer pain management. Collaborative strategies integrating Chinese and Western medicine, coupled with precision delivery technologies, are expected to advance more efficient and safer pain control, offering new approaches and methods for achieving superior pain management outcomes. Full article

The skin is exposed to many environmental stressors, such as UV rays, pollution, and smoke, and psychological stress, which can compromise its structure and function. These factors can cause premature aging, weaken the skin barrier, worsen or induce pathological conditions such as acne and eczema, hyperpigmentation, and melanoma, and slow healing. Ellagic acid (EA) is a polyphenol with various pharmacological effects important for the treatment of skin conditions. It has antioxidant, anti-inflammatory, and depigmenting properties, and it inhibits the enzyme tyrosinase, involved in melanin production, helping reduce dark spots and exhibiting antiproliferative effects against melanoma cells. With its antioxidant effect, it protects the skin against photoaging, combats oxidative stress and signs of aging, such as wrinkles and loss of elasticity, and strengthens collagen and elastin. However, the main limits of EA are its low aqueous solubility, instability, and poor skin permeability that limit its clinical efficacy. This review focuses on EA formulations developed to overcome these limitations and improve its therapeutic effects for skin diseases. Nano-delivery systems such as vesicles, lipidic and polymeric nanoparticles, nanospheres, cyclodextrins, and nanogels have been reported alongside other innovative preparations such as biscuits, sponges, and nanosheets and conventional ones such as ointments, creams, and films. Full article

Background/Objectives: A non-toxic nano-platform which can increase drug-loading rate and synergistically increase antitumor effect is very ideal. This study provides the concept that a combination of photothermal therapy with chemotherapy and anti-inflammatory therapy will be achieved by ablation of the local tumor, robust strategies for the suppression of distant tumors with enhanced antitumor therapy outcomes. Methods: In this study, the chemotherapeutic drug cisplatin (DDP) and the anti-inflammatory drug Aspirin-DL-Lysine (ADL) were loaded into a hollow porous nanomaterial zeolitic imidazolate framework-8 (ZIF-8), which was then coated with polydopamine, in order to form near-infrared absorption organic nanoparticles DDP-ADL@ZIF-8@PDA with excellent photothermal conversion efficiency. The antitumor efficacy of the nanodrug was evaluated through physicochemical characterization, cell biology studies, and animal experiments. Results: Photothermal therapy (PTT) of polydopamine combined with DDP and ADL can reduce inflammation and the immunosuppressive tumor microenvironment, and enhance antitumor effect. The results showed that the combined therapy could effectively eliminate the primary tumor, shrink the distant tumor, and inhibit the metastasis of the tumor. PTT in combination with chemotherapy and anti-inflammatory therapy can inhibit the expression of inflammatory factors, significantly reducing tumor immunosuppression by eliminating bone marrow-derived suppressor cells and increasing levels of cytotoxic T lymphocyte. Conclusions: This study successfully developed a DDP-ADL@ZIF-8@PDA nanomedicine for effective drug delivery, synergistic photothermal therapy, and anti-inflammatory attenuated immunotherapy to enhance treatment of human cervical cancer xenografts in mice. Overall, the combination of photothermal therapy with chemotherapy and anti-inflammatory therapy on a nano-platform has great potential for antitumor therapy applications. Full article

Central nervous system (CNS) diseases exhibit high incidence rates, and the blood–brain barrier (BBB) poses a major obstacle to drug delivery. Conventional drug delivery methods not only show limited therapeutic efficacy but also cause significant side effects. Intranasal administration offers a new strategy for CNS therapy by bypassing the BBB through the unique nasal-brain pathway, while nanodrug delivery systems (NDDSs) can improve drug delivery efficiency. On this basis, biomimetic drug delivery systems (BDDSs) based on cell membrane structure have been developed. The combination of nanoparticles modified by cell membranes or cell membrane-derived vesicles with carriers such as hydrogels creates a drug delivery system that utilizes a unique transnasal-to-brain pathway, opening new avenues for treating CNS disorders. This paper systematically reviews the classification, characteristics, and preparation strategies of BDDSs, while analyzing the anatomical pathways and physiological mechanisms of nasal–cerebral delivery. Furthermore, it delves into the biogenesis mechanisms of extracellular vesicles (EVs) and bacterial extracellular vesicles (BEVs). For CNS disorders, including glioblastoma multiforme (GBM), ischemic stroke (IS), Alzheimer’s disease (AD), and Parkinson’s disease (PD), this paper presents diverse applications and challenges of BDDSs in nasal–cerebral delivery. Full article

Fusobacterium nucleatum (Fn) has been increasingly recognized as a crucial mediator of colorectal cancer (CRC) biology, particularly in microsatellite-stable (MSS) tumors, where immune checkpoint inhibitors (ICIs) have shown limited efficacy. Rather than representing a passive microbial passenger, Fn actively shapes tumor behavior by adhering to epithelial cells, activating oncogenic signaling, and promoting epithelial–mesenchymal transition (EMT). At the same time, it remodels the tumor microenvironment, driving immune suppression through inhibitory receptor engagement, accumulation of myeloid-derived cells, and metabolic reprogramming of tumor-associated macrophages. These mechanisms converge to impair cytotoxic immunity and contribute to both intrinsic and acquired resistance to ICIs. Beyond immune escape, Fn interferes with conventional chemotherapy by sustaining autophagy and blocking ferroptosis, thereby linking microbial colonization to multidrug resistance. Most of these mechanisms derive from preclinical in vitro and in vivo models, where causal relationships can be inferred. In contrast, human data are mainly observational and provide correlative evidence without proving causality. No interventional clinical studies directly targeting Fn have yet been conducted. Its enrichment across the adenoma–carcinoma sequence and consistent detection in both tumor and fecal samples highlight its potential as a biomarker for early detection and patient stratification. Importantly, multidimensional stool assays that integrate microbial, genetic, and epigenetic markers are emerging as promising non-invasive tools for CRC screening. Therapeutic strategies targeting Fn are also under exploration, ranging from antibiotics and bacteriophages to multifunctional nanodrugs, dietary modulation, and natural microbiota-derived products. These approaches may not only reduce microbial burden but also restore immune competence and enhance the efficacy of immunotherapy in MSS CRC. Altogether, current evidence positions Fn at the intersection of microbial dysbiosis, tumor progression, and therapy resistance. A deeper understanding of its pathogenic role may support the integration of microbial profiling into precision oncology frameworks, paving the way for innovative diagnostic and therapeutic strategies in CRC. Full article

Background/Objectives: Understanding the interactions between nanoparticles and mucosal tissues is crucial for the development of advanced drug delivery systems, as the diffusion behavior of nanoparticles through mucus is strongly influenced by their size and surface properties, and the viscoelastic nature of the hydrogel matrix. In this study, we investigated the impact of nanoparticle size, surface charge, and hydrogel crosslinking density on nanoparticle diffusion in a mucus model in vitro. Method: Citrate-stabilized and PEGylated 30 and 100 nm gold nanoparticles were used as a model of nanoparticle and their diffusion through mucus-mimicking mucin-based hydrogels of two different crosslinking densities was assessed. Results: Citrate-stabilized 30 nm nanoparticles demonstrated greater diffusion in hydrogels mimicking native mucus compared to more densely crosslinked ones, reaching approximately 50.3 ± 0.2% diffusion within the first 5 min of the assay. This size-dependent effect was not observed for the 100 nm citrate-stabilized nanoparticles, which showed limited diffusion in both hydrogel types. To confer different surface charge, gold nanoparticles were functionalized by the conjugation of poly(ethylene glycol) (PEG) derivatives of identical molecular weight with different terminal moieties (neutral, and positively and negatively charged) to modulate the surface charge and assess their interaction with the negatively charged mucin matrix. PEGylated particles exhibited significantly greater mobility than their citrate-stabilized counterparts, regardless of size or hydrogel density owing to the muco-penetration effect of PEG. Among PEGylated particles, the neutral and negatively charged 30 nm variants demonstrated higher diffusion than the positively charged ones due to weaker interactions with the negatively charged mucin hydrogel. For the 100 nm particles, the neutral PEGylated nanoparticles exhibited greater diffusion than their positively charged counterparts. Conclusions: Overall findings could provide valuable insights into the more rational design of nanoparticle-based drug delivery systems targeting mucosal tissues. Full article

Alzheimer’s disease (AD) represents the major cause of dementia worldwide, involving different etiopathogenetic mechanisms, but with no definitive cure. The efficacy of new AD drugs is limited by the multifactorial disease nature that involves several targets, but also by the difficult penetration across the blood–brain barrier (BBB) for reaching the target area at therapeutic doses. Thus, the inability of many compounds to efficiently bypass the BBB makes it arduous to treat the disease. Furthermore, the lack of more representative BBB in vitro models than conventional 2D cultures, and xenogeneic animal models that recapitulate AD pathogenesis, makes it even more difficult to develop definitive cures. In this context, microfluidics has emerged as a promising tool, offering advanced strategies for simulating the BBB, investigating its crossing mechanisms, and developing nanocarriers that successfully pass the BBB for brain-targeting, with particular interest in pathological states. The advantages of microfluidic platforms for studying the BBB role in pathophysiological conditions might herald more tailored and effective approaches based on functionalized nanosystems for treating AD. Here, we provide an overview of the latest advances in microfluidic-based technologies both for the synthesis of nanodrug delivery systems, and for developing advanced models of the BBB-on-a-chip to simulate this biological barrier, facing open challenges in AD, and improving our understanding of the disease. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most devastating infectious diseases worldwide, with rising multidrug resistance limiting the effectiveness of conventional treatments. Novel therapeutic approaches are urgently needed to complement or replace existing regimens. Among emerging candidates, antimicrobial peptides (AMPs) stand out as versatile molecules capable of exerting direct antimycobacterial effects while also modulating the host immune response. This review explores peptide-based strategies against TB, with a focus on four major axes of innovation. First, we examine host-directed pathways, including the vitamin D–cathelicidin axis and other immunomodulatory mechanisms and their regulatory role in the induction of endogenous AMPs such as cathelicidin LL-37, which contributes to host-directed defense. Second, we discuss peptide-based vaccines designed to elicit robust and durable protective immunity, representing a complementary alternative to classical vaccine approaches. Third, we highlight the synergistic potential of AMPs in combination with first-line and second-line anti-TB drugs, aiming to restore or enhance bactericidal activity against resistant strains. Finally, we analyze technological platforms, including nanocarriers and inhalable formulations, that enable targeted pulmonary delivery, improve peptide stability, and enhance bioavailability. By integrating molecular design, immune modulation, and advanced delivery systems, peptide-based strategies provide a multifaceted approach to overcoming the limitations of current TB therapy. Collectively, these advances position AMPs not only as promising standalone agents but also as key components in combination and host-directed therapies, with strong potential to reshape the future clinical management of tuberculosis. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) exhibits pronounced biological heterogeneity, aggressive behavior, and a high risk of recurrence and metastasis. The conventional treatments for TNBC have notable limitations: surgical resection may leave residual tumor cells; chemotherapy (CT) frequently induces systemic toxicity and drug resistance; and radiotherapy damages surrounding organs and compromises the patients’ immune function. Methods: Herein, we designed a carrier-free nanodrug delivery system composed of self-assembled Curcumin nanoparticles (NPs) coated with a tannic acid (TA)/Fe(III) network (denoted as CUR@TA-Fe(III) NPs). We systematically evaluated the in vitro cytotoxicity and photothermal–ferroptosis synergistic therapeutic efficacy of CUR@TA-Fe(III) NPs in 4T1 breast cancer cells, as well as the in vivo antitumor activity using 4T1 tumor-bearing mouse models. Results: CUR@TA-Fe(III) NPs had high drug loading efficiency (LE) of 27.99%, good dispersion stability, and photothermal properties. Curcumin could inhibit the growth of 4T1 cancer cells, while TA-Fe(III) efficiently converted light energy into heat upon exposure to near-infrared (NIR) light, leading to direct thermal ablation of 4T1 cells. Additionally, TA-Fe(III) could supply Fe(II) via TA, increase intracellular Fe(II) content, and generate reactive oxygen species (ROS) through the Fenton reaction, in turn inducing lipid peroxidation (LPO), a decrease in mitochondrial membrane potential (MMP), and glutathione depletion, eventually triggering ferroptosis. Conclusions: This treatment strategy, which integrates CT, PTT, and ferroptosis, is expected to overcome the limitations of traditional single-treatment methods and provide a more effective method for the treatment of TNBC. Full article

Hemorrhagic stroke is a severe cerebrovascular disease with a high rate of disability and mortality. Its complex pathological mechanisms, such as blood–brain barrier damage, neuroinflammation, and oxidative stress, along with the restrictive nature of the blood–brain barrier, have restricted the clinical therapeutic effects of drugs. Nanotechnology, with its advantages of targeting ability, biocompatibility, and multifunctionality, has provided a new approach for the precise diagnosis and treatment of hemorrhagic stroke. In terms of diagnosis, imaging technology enhanced by magnetic nanoparticles can achieve real-time bedside monitoring of hematoma dynamics and cerebral perfusion, significantly improving the timeliness compared with traditional imaging methods. In the field of treatment, the nanodrug delivery system can remarkably improve the bioavailability and brain targeting of clinical drugs and herbal medicines by enhancing drug solubility, crossing the blood–brain barrier, and responsive and targeting drug release. Multifunctional inorganic nanomaterials, such as cerium oxide nanoparticles, graphene, and perfluorooctyl octyl ether nanoparticles, can alleviate brain edema and neuronal damage through antioxidant and anti-inflammatory effects, and the scavenging of free radicals. Moreover, gene delivery mediated by nanocarriers and stem cell transplantation protection strategies have provided innovative solutions for regulating molecular pathways and promoting nerve repair. Although nanotechnology has shown great potential in the diagnosis and treatment of hemorrhagic stroke, its clinical translation still faces challenges such as the evaluation of biosafety, standardization of formulations, and verification of long-term efficacy. In the future, it is necessary to further optimize material design and combine multimodal treatment strategies to promote a substantial breakthrough in this field from basic research to clinical application. Full article

Graphene, owing to its exceptionally high specific surface area, abundant surface functional groups, and outstanding biocompatibility, exhibits tremendous potential in the development of nanodrug delivery systems. This review systematically outlines the latest research advancements regarding graphene and its derivatives in drug loading, targeted delivery, and smart release. It covers delivery strategies and mechanisms for various types of drugs, including small molecules and macromolecules, with a particular emphasis on their applications in major diseases such as cancer, neurological disorders, and infection control. The article also discusses stimulus-responsive release mechanisms, such as pH-responsiveness and photothermal responsiveness, and highlights the critical role of surface functionalization of graphene and its derivatives in enhancing therapeutic efficacy while reducing systemic toxicity. Furthermore, the review evaluates key challenges to the clinical translation of graphene-based materials, including safety, toxicity, and metabolic uncertainties. It points out that future research should focus on integrating structural modulation of materials with biological behavior to construct intelligent nanoplatforms featuring biodegradability, low immunogenicity, and precise therapeutic targeting. The aim of this paper is to provide theoretical insights and technical guidance for the customized design and precision medicine applications of graphene and its derivative-based drug delivery systems. Full article