Search Results (904)

Breast cancer remains a major disease burden and a leading cause of cancer-related morbidity and mortality among women, while current therapies are often limited by toxicity, drug resistance, and recurrence. α-Mangostin (AM), a prenylated xanthone derived from Garcinia mangostana L., has attracted considerable interest because of its antioxidant, redox-modulating, and anticancer properties, which may contribute to improved health outcomes and patient well-being. This study systematically reviewed the therapeutic potential of AM against breast cancer based on evidence from in silico, in vitro, and in vivo studies focusing on biomedical and pharmaceutical applications. Relevant articles were retrieved from the Scopus and PubMed databases using predefined keywords and selection criteria. Eligible studies were extracted, categorized, and analyzed using Microsoft Word and EndNote to assess the pharmacological actions, target interactions, delivery systems, and therapeutic outcomes associated with AM, while the quality of animal studies was assessed using the ARRIVE guidelines. Twenty-nine studies met the inclusion criteria. Computational studies demonstrated favorable AM interactions with ERα, STAT3, RXRα, CXCR4, AKT1, CTNNB1, and HSP90AA1. In vitro studies showed that AM inhibited cancer cell viability, induced apoptosis and autophagy, modulated reactive oxygen species, and suppressed metastatic and immune-evasion markers. Furthermore, nano-formulations, radiolabeled derivatives, and combination approaches improved bioavailability, tumor targeting, and efficacy. In vivo studies reported inhibition of tumor-growth and metastasis, improved pharmacokinetic profiles, and prolonged survival. However, no clinical trials evaluating AM in breast cancer patients have been reported to date. Overall, AM represents a promising preclinical candidate for breast cancer treatment. Nevertheless, standardized pharmacokinetic, toxicological, and efficacy studies, followed by well-designed clinical trials, are essential to facilitate its translation into clinical practice. Full article

Background: Triple-Negative Breast Cancer (TNBC) remains the most aggressive oncological challenge within the African continent, characterized by high molecular heterogeneity, early onset in African women, and the absence of hormonal receptors. Multi-drug resistance (MDR), driven by ATP-binding cassette (ABC) efflux pumps and supported by the persistence of cancer stem cells (CSCs) within the tumor microenvironment, significantly compromises clinical outcomes and traditional treatment efficacy. Objective: This systematic review evaluates the ethnobotanical relevance, phytochemical diversity, and toxicity of some medicinal plants from the African pharmacopoeia specifically utilized or investigated for their activity against the TNBC phenotype. Methods: Following PRISMA guidelines, a systematic search was executed across PubMed, ScienceDirect, Scopus, Web of Science, and AJOL. The study focuses on original research published between 2011 and 2026 utilizing TNBC-specific models (such as MDA-MB-231, BT-20, HCC1937, or 4T1) and analyses the growth habits, parts used, and traditional administration modes of the selected African plant species, distributed across Western, Central, Southern, and Eastern Africa. Following a rigorous multi-reviewer screening process, a final set of 52 primary articles representing 30 distinct genera and 22 botanical families was selected for qualitative and quantitative synthesis. Results: This review identifies plant species actively used or studied in Africa for their anti-TNBC potential, with the most representative botanical families being Asteraceae (13%), Fabaceae (7%), and Annonaceae (7%). These species are traditionally administered through various methods, including decoction, infusion, and mastication, utilizing diverse plant parts such as leaves, stem and root barks. Significant cytotoxic activities against TNBC cell lines (notably MDA-MB-231) were recorded, with IC₅₀ values as low as 5.10 ± 0.28 µg/mL for Catharanthus roseus and 13.56 µg/mL for Nauclea pobeguinii. Furthermore, species such as Vernonia amygdalina and Curcuma longa demonstrated a capacity to enhance the effectiveness of conventional chemotherapy like Doxorubicin, suggesting a strong potential for chemosensitization and therapeutic synergy in managing resistant breast cancer phenotypes. Conclusions: Standardized African phytomedicines represent a promising frontier in overcoming TNBC chemoresistance. However, the lack of clinical trials and end-to-end drug development infrastructure on the continent remains a significant barrier. Transitioning to nano-formulated delivery systems and establishing regional drug discovery hubs under the ethical framework of the Nagoya Protocol are essential steps toward developing precise and equitable oncology treatments from Africa’s rich biodiversity. Full article

Conventional antibiotics exhibit limited ability to penetrate host cell membranes, making intracellular bacterial infections difficult to eradicate completely. As naturally derived nanoscale membrane structures, bacterial extracellular vesicles (EVs) possess excellent biocompatibility and intrinsic transmembrane transport capability, thereby demonstrating unique advantages for in vivo drug delivery. The present study investigated the feasibility of using EVs derived from the avirulent Streptococcus suis T15 as novel carriers for ciprofloxacin delivery. We also comprehensively evaluated the biosafety and anti-infective efficacy of this nanodrug delivery system in vitro and in vivo. Cytotoxicity assays, live/dead cell staining, and hemolysis analyses demonstrated that T15-derived EVs at concentrations below 50 μg/mL did not cause significant cellular damage or hemolysis. Serum biochemical analyses in mice further confirmed the absence of obvious organ toxicity, indicating favorable biosafety within the tested concentration range. Ciprofloxacin was successfully loaded into EVs using a combination of ultrasonication and electroporation, achieving a drug concentration of 438.6 μg/mL and a loading efficiency of 10.96%. The ciprofloxacin-loaded EVs (EV-CIP) exhibited significantly greater antibacterial activity than free ciprofloxacin against both intracellular bacteria and fluoroquinolone-resistant strains exhibiting efflux pump activity. Evaluation in animal infection models showed that EV-CIP markedly reduced mortality in infected Galleria mellonella larvae. It also decreased bacterial burdens in multiple mouse organs and significantly alleviated histopathological damage. These results collectively suggest that EVs derived from the avirulent S. suis T15 were safe and effective within the tested concentration range and experimental conditions. The EV-based ciprofloxacin delivery system substantially enhanced the clearance of intracellular pathogens and fluoroquinolone efflux pump-positive bacteria, suggesting its potential application in the treatment of difficult-to-treat bacterial infections. This study provides a theoretical and experimental basis for the further development of novel EV-based anti-infective drug delivery strategies for livestock and poultry. 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

Xanthohumol (XN), a prenylated chalcone isolated from Humulus lupulus L., exhibits a wide range of biological activities, including antioxidant, anti-inflammatory, and chemopreventive effects. However, its therapeutic application is limited by poor aqueous solubility, low chemical stability, and rapid clearance from the systemic circulation. The present study aimed to develop and characterize a novel nano-sized drug-delivery system for XN that combines favourable colloidal stability, efficient encapsulation, sustained release, and reduced recognition by macrophages (“stealth-like” properties). To achieve this, XN-loaded cationic liposomes were coated with two marine polysaccharides, iota-carrageenan (CAR) and fucoidan (FUC), followed by Ca²⁺-mediated cross-linking. Liposomes were prepared by the ethanol injection method, and formulation parameters were optimized using a 2³ + 1 full factorial design. Surface modification and cross-linking conditions were further optimized through polyelectrolyte titration and a Taguchi L9 orthogonal array. The resulting nanocarriers were evaluated for particle size, polydispersity, ζ-potential, encapsulation efficiency, release behavior, and cellular uptake. Both coatings significantly prolonged XN release compared with uncoated liposomes, with CAR-coated vesicles providing the most sustained release (≈55% over 48 h). In RAW264.7 macrophages, 50 µg/mL CAR-coated liposomes reduced cellular uptake by approximately 74% following 1-h incubation relative to uncoated controls and maintained this reduction over 2 h whereas FUC-coated vesicles afforded only transient early evasion. The cross-linked iota-carrageenan coating thus represents a promising strategy for conferring stable “stealth-like” characteristics to XN-loaded liposomes intended for prolonged drug delivery. Full article

Background: Actinium-225 (²²⁵Ac) is receiving major attention as the radionuclide of choice for targeted alpha therapy (TAT) due to its outstanding physical properties such as a long physical half-life of 9.9 days and a short range of alpha (α)-particles which are responsible for the destruction of malignant tumors, whilst sparing normal surrounding tissues. Although the physical properties of ²²⁵Ac make it a desirable radionuclide for TAT, its application is challenging due to the lack of chelators available to stabilize its daughter radionuclides, resulting in the recoil effect. This occurs when there is a breakdown between the radionuclide and the chelator, therefore minimizing the therapeutic effects of the radiopharmaceutical. Nanodrug delivery systems (NDDSs) may minimize the challenge of ²²⁵Ac’s recoiling daughters and increase tumor penetration. Aim: This study aimed at using poly(lactic-co-glycolic)acid (PLGA) and chitosan (CS) nanoparticles as a delivery vehicle for targeted alpha therapy of prostate cancer in order to increase the therapeutic effect of ²²⁵Ac PSMA617-TFA. Methods and Results: PLGA nanoparticles were prepared using a nanoprecipitation method, after which they were functionalized with chitosan and folic acid. Following synthesis of ²²⁵Ac PSMA617-TFA, the radiopharmaceutical was loaded onto the nanoparticles. SEM analysis and FTIR were performed for characterization of the nanoparticles, and in-vitro drug release of ²²⁵Ac PSMA617-TFA at pH = 6.5 and pH = 7.4, respectively, was measured. The nanoparticles prepared had an average size of 200 nm and had a positive charge. This was further confirmed using a zetasizer and with scanning electron microscope (SEM) analysis. The PLGA-CS nanoparticles indicated a high encapsulation efficiency after 24 h. The results also showed a controlled release of ²²⁵Ac PSMA617-TFA over 72 h. The results of this study indicate that PLGA-CS nanoparticles are suitable for retaining ²²⁵Ac and its recoiling daughters (²²¹Fr and ²¹³Bi) at the tumor site, potentially providing a platform for future therapeutic evaluation. Conclusions: The results of this study indicate that PLGA-CS nanoparticles demonstrate feasibility as a drug delivery vehicle for ²²⁵Ac PSMA617-TFA, with effective retention of ²²⁵Ac and its decay daughters. However, biological validation through in vitro cellular studies and in vivo preclinical models is required before therapeutic effectiveness can be established. Full article

Acute otitis media is an inflammatory disease affecting all compartments of the middle ear, characterized by localized pain, fever, hearing impairment, and, occasionally, purulent exudate. It represents a significant clinical concern in both pediatric and adult populations, with approximately 709 million cases reported annually worldwide, 51% of which occur in children. However, currently available topical otic formulations are limited by their inability to achieve predictable therapeutic concentrations at the site of inflammation, resulting in reduced efficacy. In addition, the selection of appropriate active pharmaceutical ingredients (APIs) for drug products remains challenging; as a result, existing therapies do not comprehensively address all stages of pathogenesis. This study aimed to analyze existing locally acting formulations for middle ear drug delivery, evaluate their advantages and limitations, and assess modern approaches to the development of novel drug delivery systems and API combinations. A critical review of 69 publications (2010–2026) was conducted, supplemented by a strengths and limitations analysis of dosage forms and an evaluation of APIs based on clinical data. The findings highlight a lack of targeted drug delivery systems, limited efficacy of existing API combinations against bacterial biofilms, and their risk of ototoxicity. Emerging innovative drug delivery approaches, including microemulsions, vesicular systems, stimuli-responsive systems, and hydrogels, have demonstrated promising results in preclinical studies; however, their efficacy and safety remain to be confirmed in clinical settings before their full therapeutic potential in otitis media treatment can be realized. Full article

Background/Objectives: Micro- and nano-scale hydrogels (microgels and nanogels) have attracted increasing attention as carriers for drug delivery due to their high-water content, responsiveness to external stimuli, tunable properties, and versatility. In this work, gelatin methacryloyl (GelMA) with a medium degree of methacryloylation (DoM ca. 60%) was ad hoc synthesized as a constituent material for nanogel production. For the first time in the literature, GelMA-based nanogels (nanoGelMA) were developed through an optimized two-step desolvation method combined with photo-crosslinking. Methods: The influence of key process parameters, including the pH, volume of desolvating agent, photo-initiator concentration, and UV exposure time, was systematically investigated to identify optimal conditions for nanoGelMA preparation. To assess its potential as a drug delivery nanocarrier, the nanoGelMA was loaded with ibuprofen (IBU) as a model anti-inflammatory drug via in situ encapsulation during nanogel preparation. Results: The formulated nanoGelMA exhibited an average hydrodynamic diameter (d) of ca. 250 nm, a polydispersity index of 0.2, and a production yield of approximately 30%. The nanogels demonstrated stability in water and in phosphate buffer at pH 5 over 96 h, while exhibiting significant swelling in physiological-like conditions and enzymatic degradation (d of ca. 421 ± 91 nm and 609 ± 182 nm at 96 h, respectively). The cytocompatibility evaluation demonstrated high cell viability (86–96%) of the nanoGelMA at different concentrations (1–5 mg/mL). IBU-loaded nanoGelMA particles were successfully developed via direct drug encapsulation during nanogel formation, achieving a maximum encapsulation efficiency of ca. 30%, and exhibited environment-responsive release, with kinetics modulated by the ionic strength, pH, and enzymatic activity. Conclusions: Overall, the nanoGelMA developed herein represents a promising nanogel platform with great potential for the development of advanced and controlled drug delivery therapies. Full article

Mesoporous silica nanoparticles (MSNs) are promising nanomaterials for many applications, including water remediation, owing to their high surface area, tunable mesoporosity, and modifiable silanol-rich surfaces. However, their conventional synthesis often relies on costly tetraethyl orthosilicate (TEOS), cationic surfactants, organic solvents, and energy-intensive hydrothermal processing. Herein, a facile sustainable room-temperature sol–gel route is reported using inexpensive sodium silicate as the silica source, L-ascorbic acid as a mild biodegradable acid catalyst, and a binary nonionic surfactant system, Triton X-100/polysorbate 80, as the structure-directing template. The method replaces alkoxysilanes and hazardous cationic templates and eliminates external heating. It enables the production of uniform spherical MSNs with a locally ordered mesoporous structure, high specific surface area up to 551.5 m² g⁻¹, and large pore volume up to 1.98 cm³ g⁻¹. The adsorption capability of the optimized MSNs as nano-adsorbents was demonstrated using amoxicillin (AMX) as a model pharmaceutical contaminant. The optimized sample showed maximum AMX uptake at pH 5.0, followed pseudo-second-order kinetics, and fitted the Langmuir isotherm with a monolayer capacity of 91.3 mg g⁻¹. In spiked water matrices, the optimized MSNs recovered 88.5% and 84.4% of AMX from tap water spiked at 10 and 50 mg L⁻¹, respectively, and 83.5% and 81.0% from synthetic municipal wastewater spiked at the same concentrations, with RSD values below 5%. The adsorbent further retained 94% of its initial capacity after five adsorption–desorption cycles. This work establishes a scalable green route for producing high-quality MSNs and demonstrates the feasibility of the resulting silanol-rich mesoporous nano-adsorbents for pharmaceutical micropollutant removal, while also indicating their potential suitability as carrier platforms for drug-delivery applications. Full article

The rapid rise of antimicrobial resistance (AMR) has created an urgent need for innovative therapeutic strategies beyond conventional antibiotics. Smart nano-antibiotics have emerged as advanced antimicrobial systems capable of improving drug delivery, enhancing pathogen targeting, overcoming biofilm-associated resistance, and reducing systemic toxicity. This review discusses recent progress in stimuli-responsive nanoplatforms, including pH-responsive, enzyme-responsive, temperature-sensitive, and redox-activated systems for precision antimicrobial therapy. The role of artificial intelligence in nanomaterial design, toxicity prediction, drug release optimization, and personalized treatment development is also critically examined. Furthermore, the review highlights targeted antimicrobial delivery, multifunctional nano-drug combination systems, biosensor integration, and autonomous AI-driven therapeutic platforms for combating multidrug-resistant infections. Current challenges related to toxicity, regulatory limitations, scalability, and AI data reliability are discussed alongside emerging clinical and industrial developments. Smart nano-antibiotics represent a promising next-generation approach for improving precision antimicrobial therapy and addressing the growing global burden of antimicrobial resistance. Full article

Keratoconus, a progressive corneal ectasia, remains a major cause of irreversible visual impairment worldwide. Conventional corneal cross-linking (CXL) with riboflavin/ultraviolet A (UVA) has revolutionized clinical management, yet its efficacy is still constrained by epithelial barriers, oxygen dependence, and safety concerns in thin corneas. Emerging nanotechnology provides a transformative opportunity to overcome these bottlenecks. This review highlights the enhancement of riboflavin delivery efficiency by nanocarriers, the photodynamic optimization of nano-enhanced cross-linking agents, and the synergistic strengthening effect of nanocomposites on corneal mechanical strength. We emphasize not only their potential to enhance drug penetration, improve cross-linking efficiency, and extend clinical indications, but also their role in advancing toward a new generation of personalized, intelligent, and minimally invasive corneal therapy. Finally, we discuss translational challenges, including manufacturing, long-term biosafety, and regulatory frameworks, and present a theoretical roadmap that integrates nanotechnology, real-time imaging, and artificial intelligence (AI)-assisted decision-making to achieve a closed-loop “sense–decide–act” therapeutic system. By situating nanomaterial-enhanced CXL within precision ophthalmology, this review highlights its capacity to redefine the standard of care for keratoconus and related ectatic disorders. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a complex etiology and a protracted disease course. Active ingredients from traditional Chinese medicine (TCM), by leveraging the holistic regulatory advantages of anti-inflammatory activity, immune barrier preservation, and gut microbiota regulation, have shown unique therapeutic potential in the intervention of UC. Although bottlenecks such as unclear targets, fragmented mechanisms of action, and poor druggability constrain the clinical translation of TCM active ingredients, current research efforts are dedicated to overcoming these obstacles. This article reviews the latest research progress (2021–2026) on TCM active ingredients for UC treatment. It analyzes the anti-UC mechanisms from three core dimensions: chemical diversity and pharmacodynamic characteristics, validation of direct targets, and indirect regulation through the “gut microbiota–metabolite” axis. Moreover, it emphasizes recent breakthroughs in druggability optimization technologies, including carrier-based nano drug delivery systems (NDDS), carrier-free NDDS, co-delivery NDDS, and prodrug design strategy. Research demonstrates that TCM active ingredients achieve therapeutic effects by modulating inflammatory signaling networks, restoring intestinal immune homeostasis, repairing the mucosal barrier, and remodeling the gut microenvironment. Simultaneously, the application of novel delivery strategies effectively resolves issues such as poor solubility, low oral bioavailability, and insufficient colon targeting. Finally, this review suggests that future research on TCM active ingredients for UC therapy should concentrate on systematically clarifying multi-level mechanisms and designing clinically translatable smart drug delivery strategies, aiming to provide a theoretical basis and practical reference for promoting TCM modernization and innovative UC drug development. Full article

Usnic acid (UA), a prominent lichen secondary metabolite, exhibits a unique dual therapeutic profile in dermatology, though its clinical translation is limited by systemic hepatotoxicity and poor solubility. This review comprehensively evaluates the topical efficacy, molecular mechanisms, and advanced formulation strategies of UA enantiomers and UA-rich extracts. A literature search across PubMed, Scopus, and Google Scholar identified 36 original publications focusing on anti-melanoma activity, photoprotection, and tissue regeneration. In vitro studies demonstrate that UA induces apoptosis in resistant melanoma cell lines (A375, HTB-140) via extrinsic/intrinsic pathways, with (−)-UA effectively overcoming doxorubicin resistance. Conversely, in non-cancerous models, low concentrations of UA accelerate wound and burn healing by upregulating vascular endothelial growth factor (VEGF), stimulating fibroblast proliferation, and optimizing extracellular matrix remodeling while preventing hypertrophic scarring. To mitigate skin sensitization and systemic risks, advanced drug delivery systems—including liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds—have been developed, significantly enhancing skin permeability and localized dermal retention. Ultimately, the development of bio-functionalized smart dressings and targeted nano-formulations represents the most viable path toward unlocking the full clinical potential of UA in modern dermatological and oncological care. Full article

Prostate cancer remains a major therapeutic challenge, particularly after progression to castration-resistant disease, where persistent androgen receptor signaling, metabolic adaptation, immune escape, and treatment resistance jointly limit clinical benefit. Regulated cell death (RCD) is increasingly recognized not only as an endpoint of tumor cell elimination but also as a dynamic regulator of prostate cancer progression, therapeutic vulnerability, and tumor–immune interactions. In this review, we propose an immunometabolic framework in which androgen receptor signaling, lipid and redox metabolic reprogramming, oxidative stress, and therapeutic pressure converge to shape the susceptibility of prostate cancer cells to distinct RCD modalities. We focus on autophagy and ferroptosis as two extensively studied and translationally relevant pathways, while also discussing emerging roles of necroptosis, pyroptosis, and cuproptosis. Particular attention is given to how RCD-associated signals, including damage-associated molecular patterns, inflammatory mediators, and lipid peroxidation products, may remodel the tumor immune microenvironment and influence the transition between immune-cold and immune-inflamed phenotypes. We further summarize RCD-targeted therapeutic strategies, including ferroptosis induction, autophagy inhibition, nanodrug delivery systems, rational combination therapy, and biomarker-guided patient stratification. Finally, we discuss key translational barriers, including context-dependent biological effects, limited clinical validation, tumor heterogeneity, adaptive resistance, and insufficient predictive biomarkers. By integrating cell death biology with metabolic reprogramming, immune remodeling, and therapeutic resistance, this review highlights RCD as a promising but context-dependent therapeutic vulnerability in advanced prostate cancer. Full article

The combination of chemotherapy and immunotherapy represents a promising approach that leverages their complementary benefits. However, the side effects resulting from off-target effects and the low efficiency of immune activation remain a significant concern. Herein, we developed a zinc-doped calcium phosphate (ZCP) nanocarrier for the delivery of the chemotherapeutic drug doxorubicin (DOX). By further encapsulating whole proteins from 4T1 breast cancer cells, we constructed a novel nanodrug delivery system named ZCPDM. This system enables specific targeting of tumor cells and undergoes intracellular degradation to release DOX, Zn²⁺, and Ca²⁺. As a chemotherapeutic agent, DOX induces apoptosis while significantly elevating intracellular reactive oxygen species (ROS), thereby enhancing cytotoxicity. This leads to DNA damage and the release of chromosomal fragments. These DNA fragments, together with Zn²⁺, activate the cGAS-STING signaling pathway and trigger pyroptosis, which promotes more efficient recognition and clearance of tumor cells by the immune system. Through these dual mechanisms, ZCPDM effectively combines chemotherapy and immunotherapy. The anti-tumor efficacy and underlying mechanisms were validated at the cellular level. Furthermore, studies in tumor-bearing mice demonstrated its robust anti-tumor performance and ability to suppress tumor recurrence, along with good biosafety. This targeted drug delivery system achieves safe and synergistic chemo-immunotherapy through homologous targeting-mediated pyroptosis and activation of the cGAS-STING pathway, offering a novel and promising strategy for cancer treatment. Full article