Self-crosslinked fucoidan nanoparticles via electron beam irradiation: Synthesis, physicochemical analysis, and drug delivery application

Yolk@shell nanostructures have emerged as promising platforms for biomedical applications due to their unique architecture, which combines the high surface area and loading capacity of hollow nanoparticles with the structural stability and functional versatility of core@shell systems. In this work, we report the synthesis of multifunctional Au@MnFe-Prussian Blue Analog (PBA) yolk@shell nanostructures through a two-step process: initial formation of Au@PBA core@shells, followed by selective leaching of the inner PBA shell. This process not only generates a well-defined internal cavity of ∼75nm, enhancing drug-loading capacity, but also induces partial etching of the gold core and its redeposition onto the PBA shell. This redistribution of gold leads to the emergence of absorbance in the near-infrared (NIR) region, enabling efficient photothermal conversion. Meanwhile, the MnFe PBA shell offers pH-sensitive properties and excellent biocompatibility. Using doxorubicin (DOX) as a model chemotherapeutic, the system exhibits a loading efficiency of ∼50% and a pH-dependent release profile, with enhanced release (∼150%) under NIR irradiation. In vitro studies demonstrate effective cellular uptake and synergistic cytotoxicity upon combined chemo- and photothermal treatment. This study reveals the significant potential of Au@MnFe PBA yolk@shell architectures for controlled drug delivery.

Onychomycosis is a common fungal nail infection, causing nail thickening and discoloration. Tavaborole, a topical antifungal, has fewer side effects but requires long treatment periods and often results in low cure rates. In this study, we developed a Zn2+-driven tavaborole-adenosine (AT-Zn2+) hydrogel to improve its therapeutic effect. The hydrogel enhanced tavaborole's solubility, drug loading, and antifungal activity. Characterization by nuclear magnetic resonance (NMR), ultraviolet-visible (UV-vis) spectroscopy, and transmission electron microscopy (TEM) confirmed its successful synthesis and nanofiber structure. In vitro release tests showed that about 65% of tavaborole was released in PBS at pH 5.5 over 24 h, indicating pH-sensitive drug release for targeted therapy. Permeation studies using a bovine hoof model showed effective tavaborole penetration through keratinized tissues with a steady-state flux of 162 μg/cm2/h. The AT-Zn2+ hydrogel demonstrated lower minimum inhibitory concentrations (MICs) for C. albicans (0.00156 mM) and A. fumigatus (0.025 mM) compared to those of tavaborole alone. In a bovine onychomycosis model, the hydrogel showed stronger antifungal effects than the tavaborole solution. Cytotoxicity assays on RAW 264.7 cells indicated good biocompatibility with >85% cell viability. These findings suggest that the AT-Zn2+ hydrogel holds significant potential as a clinically effective antifungal agent.

The development of multifunctional host materials capable of simultaneous diagnostics and therapy holds significant promise for biomedical applications. Here, we report the synthesis of NaYF4:Yb,Er particles with cuboidal morphology, designed for optical temperature sensing. To enable controlled drug release, the hydrophobic particles were coated with a mesoporous silica layer to enhance biocompatibility and facilitate dispersion in aqueous solutions and also allowed loading the hybrid material with drug molecules. Surface functionalization with folic acid (FA) further enhanced their potential for targeted delivery applications. Doxorubicin, a chemotherapeutic agent, was successfully loaded into the mesoporous silica shell, allowing for pH-sensitive drug release. Ratiometric upconversion luminescence in both the visible and near-infrared I (NIR-I) region allowed precise temperature monitoring under NIR excitation. The thermometric performance of this system was also evaluated in chicken breast tissue. This work highlights the potential of these hybrid particles as a versatile platform for integrated temperature sensing and drug delivery, with promising applications in theranostics.

Thrombolytic therapy, exemplified by tissue plasminogen activator, is often constrained by a short half-life, non-specific activity, and bleeding risks. To address these limitations, we developed tLipo@UA, a fibrin-targeted and pH-responsive liposomal system for the co-delivery of the urokinase-type plasminogen activator (uPA) and aspirin (acetylsalicylic acid, ASA). This system was functionalized with the CREKA (Cys-Arg-Glu-Lys-Ala) peptide for specific thrombus homing, and cholesteryl hemisuccinate (CHEMS) was incorporated to enable pH-sensitive drug release within the acidic thrombotic microenvironment. Experiments conducted both in vitro and in vivo demonstrated that tLipo@UA achieved efficient thrombus targeting and responsive drug release. The released uPA effectively dissolved thrombi, while the co-delivered ASA modulated the thrombotic microenvironment by suppressing the inflammatory cytokine release, thereby exhibiting synergistic thrombolytic and anti-inflammatory effects. Encapsulation of uPA significantly prolonged its circulation time and enhanced its localized efficacy. Furthermore, this system showed a favorable biosafety profile. Collectively, tLipo@UA presents a promising strategy for enhancing thrombolytic potency and achieving microenvironment reprogramming with reduced off-target risks, offering a rational design for dual-function drug carriers in the treatment of thrombotic diseases.

Targeted cross-linking tumor extracellular matrix by genipin and doxorubicin co-loaded nanomedicine to efficiently inhibit tumor metastasis.

The abuse of antibiotics has accelerated the emergence of multidrug-resistant (MDR) bacterial strains, while the development of novel antibiotics has failed to keep pace with the evolution of bacteria. Consequently, there is an urgent need to develop innovative alternative antibacterial materials to combat drug-resistant bacterial infections. Herein, we fabricate Cu2+-doped hollow Ca2+-tannic acid nanoparticles (ATA@Cu NPs) with pH-sensitive drug release behavior to effectively eliminate MDR bacteria at acidic infection sites. Under a pH 6.0 environment that simulates the infection microenvironment, the ATA@Cu NPs can release the Cu2+ to potently eradicate methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MRPA). Notably, owing to the excellent intracellular drug delivery property, ATA@Cu NPs exhibit potent bactericidal efficiency against intracellular bacteria. Furthermore, the ATA@Cu NPs demonstrate commendable therapeutic performance in treating MRPA-infected keratitis, as they significantly alleviate the bacterial burden by diminishing 4.0 logs of MRPA, promote the recovery, and restore normal corneal structure. Additionally, using a self-made nebulization device, the ATA@Cu NPs display robust therapeutic efficiency in combating MRSA-induced pneumonia and eliminating intracellular MRSA with a 2.8 log reduction via pulmonary delivery. Therefore, this study fabricates pH-responsive Cu2+-doped hollow Ca2+-polyphenol nano-therapeutics to combat MDR bacteria-induced infection, thereby providing a potential therapeutic strategy to address the challenges of MDR bacteria in the future.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s12951-025-03887-w.

The study aimed to evaluate the multifunctional therapeutic potential of PTX/Mo2CTx-MXene@Fuc combinations, emphasizing their performance in drug loading, release kinetics, oxidative stress induction, apoptosis, cell migration, and angiogenesis inhibition in cancer therapy. Mo2CTx-MXene@Fuc were synthesized and loaded with the chemotherapeutic drug Paclitaxel (PTX) to achieve pH- and NIR-responsive release. In vitro cytotoxicity, ROS generation, apoptosis, migration, and tube-formation assays were performed on cancer (4T1, MDA-MB-231) and normal (L929) cell lines under NIR (808 nm) irradiation. The nanosheets exhibited high PTX loading efficiency (85-90%) and pH-sensitive drug release, with accelerated release in acidic tumor-mimicking environments. NIR irradiation significantly enhanced ROS production in cancer cells while maintaining low oxidative activity in normal cells. Apoptosis assays confirmed pronounced cell death under NIR+ conditions, while migration and tube-formation analyses revealed that MXene nanosheets moderately inhibited cell motility and suppressed endothelial angiogenesis. These results demonstrated synergistic enhancement of photothermal, photodynamic, and chemotherapeutic effects. The findings indicate that PTX/Mo2CTx-MXene@Fuc nanosheets function as a multifunctional nanoplatform combining chemo-, photothermal-, and photodynamic-therapy mechanisms. Their selective cytotoxicity, ROS-mediated apoptosis, and anti-angiogenic activity highlight their strong potential for future targeted cancer therapy applications.

This study evaluated two novel combination therapies using 5-Fluorouracil (5-FU), Thymoquinone (TQ), and cockle shell - derived calcium carbonate nanoparticles (CaCO3 NPs) against HT-29 colorectal cancer (CRC) cells under hyperglycemic conditions. 5-FU and TQ were successfully encapsulated into CaCO3 NPs through encapsulation at various drug-to-nanoparticle ratios. Physicochemical characterization was performed to confirm the morphology, and particle stability. Drug release studies assessed pH-responsive behavior, while biocompatibility was evaluated on NIH/3T3 cells. Cytotoxicity and cell cycle analyses were conducted on HT-29 cells under glycemic and hyperglycemic conditions. High encapsulation efficiency was achieved at a 1:5 drug-to-nanoparticle ratio while maintaining the aragonite structure and stable physicochemical properties. The nanoformulations exhibited pH-sensitive drug release with enhanced release at acidic pH (4.8), simulating the tumor microenvironment. Improved biocompatibility and reduced toxicity were observed in normal NIH/3T3 cells compared to free drugs. Both 5-FU:TQ-CaCO3 NPs and 5-FU-CaCO3 NPs:TQ combinations significantly inhibited HT-29 proliferation and induced G1 cell cycle arrest, especially under hyperglycemic conditions. Combination index analysis confirmed synergistic effects of both treatments. The findings suggest the potential therapeutic efficacy of 5-FU:TQ-CaCO3 NPs and 5-FU-CaCO3 NPs:TQ in treating CRC associated with hyperglycemia and demonstrate the capability of biogenic CaCO3 NPs to effectively deliver chemotherapeutic agents of different polarity with minimal toxicity.

Chitosan/dialdehyde starch coating onto l-tyrosine and curcumin intercalated layered double hydroxide for improved the therapeutic effects of breast cancer.

Ambidextrous approach of silver decorated polydopamine-zinc oxide nanohybrid for long-lasting ROS generation and efficient drug delivery in tumor therapy.

Cancer recurrence remains a major challenge in postoperative treatment, often due to incomplete surgical resection and the limited effectiveness of conventional chemotherapy. Traditional drug delivery systems show significant limitations, particularly in ensuring sustained local drug release and effective adhesion to irregular tissue surfaces. To address these issues, this study presents an approach for localized cancer therapy using in situ-forming hydrogels that combine injectability, bioadhesion, self-healing properties, and responsiveness to the tumor microenvironment (TME). The hydrogels are based on hyaluronic acid (HA) derivatives, functionalized to impart distinct properties. A hyaluronic acid aldehyde derivative grafted dopamine (HA-ALD-DOPA), which provides bioadhesive characteristics, ensuring the hydrogel's attachment to postoperative sites and preventing displacement due to physiological movements and a HA aldehyde Doxorubicin derivative (HA-ALD-DOXO) loaded with the anticancer drug doxorubicin were both crosslinked with the HA diethylenetriamine derivative (HA-DETA) forming a dynamic Schiff base based platform that contribute to the hydrogel's self-healing and pH-sensitive drug release behaviors. The hydrogels exhibited shear-thinning behavior for easy injectability while maintaining mechanical integrity. In vitro drug release studies confirmed the pH-responsive nature of the system, with controlled release at physiological pH and fast release under acidic conditions, simulating the TME.

Among cancers, liver cancer is the fourth leading cause of mortality worldwide and drawbacks of conventional approaches could not inhibit this cancer. Thus, an efficient folic acid (FA)-functionalized chitosan (CS)-poly lactic-co-glycolic acid (PLGA) nanocarrier was fabricated for delivery of sodium butyrate (NB) therapeutics to HepG2 liver cancer cells. The fabricated CS-NB-PLGA-FA nanocarrier was characterized by FT-IR, DLS, TEM, and TGA. A size range of 45 nm to 80 nm, surface charge of 4.2 mV, and drug encapsulation of 15.17% were measured for nanocarrier. Controlled (about fivefolds within 2 h) and pH-sensitive drug release manner observed in PBS as well. The MTT assay indicated that CS-NB-PLGA-FA resulted in about 13% cell viability after 24 h of treatment with 400 nM concentrations (IC50: 300 nM). The qRT-PCR technique revealed nearly a 7.9- and 5.8-fold increase for Caspase9 and Bax genes while a decrease of about fivefold for the Bcl2 gene after treatment with CS-NB-PLGA-FA. Additionally, about 60% apoptosis was observed for the cells treated with nanocarrier. Remarkable enhancement did indicate for ROS (increase in the catalase and SOD units). These data have demonstrated that CS-NB-PLGA-FA could be a promising candidate against liver cancer.

Encapsulation of doxorubicin in magnesium acetate liposomes as a pH-sensitive drug carrier for tumor therapy

Methotrexate-encapsulated solid lipid nanoparticles (MTX-SLNs) and lactoferrin-decorated MTX-loaded nanoparticles (MTX-Lf-SLNs) present a promising strategy for treating colorectal cancer. Among different molecular targets, MTX demonstrated the highest affinity for Caspase-6, exhibiting a docking score of -9.316, while molecular dynamics validated stable interactions. The optimized nanoparticles displayed a spherical shape (~ 160 nm, as observed in TEM images) with a high drug encapsulation efficiency of 85.87% for MTX-SLNs and 80.11% for MTX-Lf-SLNs, which ensured improved stability. Structural analyses using FTIR, DSC confirmed effective drug encapsulation and the binding of lactoferrin. Interestingly, MTX-Lf-SLNs demonstrated higher cytotoxicity (IC50: 0.51 µM) compared to MTX-SLNs and free MTX, inducing apoptosis and stopping cell cycle progression in HCT116 cells. This improved effect was associated with receptor-driven absorption through lactoferrin targeting. Nanoparticulate formulations decreased TNF-α (17.6 ± 2.1 pg/mL), IL-6 (20.2 ± 1.9 pg/mL), and IL-1β (15.4 ± 3.4 pg/mL), thereby reducing immune activation. The nanoparticles exhibited extended, pH-sensitive drug release (70% at pH 5.7) and significant anti-angiogenic effects (~ 70% inhibition in CAM assay). Moreover, they enhanced the balance of reactive oxygen species and safeguarded mitochondria, thereby lowering overall toxicity. Migration assays further validated their capacity to obstruct cancer cell invasiveness, suggesting a potential to impede metastasis. Utilizing the bioactivity of lactoferrin for precise delivery, MTX-Lf-SLNs offer an attractive approach to enhance anti colon cancer efficacy while reducing unwanted side effects.

Abstract Micelle has been considered as a promising candidate for stimuli responsive drug delivery for target specific and sustain release. Especially, pH sensitive micelles composed of polymers, surfactant, and fatty acids are emerging as chemotherapeutic platform, providing a tool for accumulation in cancer cells. Here, we present low pH sensitive hybrid mixed micelles with enhanced stability and efficiency. It is noted that sodium dodecyl sulphate (SDS) improves the stability of Tween 20 micelles which in turn develops nonionic‐anionic mixed micelles. Further, gold nanoparticles have been attached with micelles to increase their capacity to load drug or other molecules. The proposed hybrid nano‐composite has been loaded with doxorubicin for the application of pH sensitive drug release. Drug loading and release were evaluated based on UV–vis spectrum analysis. The result shows that the developed nanocomposite loads less drug than pure mixed micelle but releases more drug at pH 4. Three different pH (4, 7.4, 10) were considered for drug release study and the nanocomposite was successful in delivering the loaded drug at pH 4 (79%) and 7.4 (70%). The improved delivery at specific pH with stability demonstrates that the hybrid mixed micelle can be a potential nano‐carrier for target specific drug delivery.

Objective The major objective of this study is to develop and evaluate phenyl boronic acid (PBA) conjugated solid lipid nanoparticles (SLNs) (PBA-SUL@SLN) for the targeted delivery of sulindac (SUL) to breast cancer (BC) cells. Significance Utilizing a dual approach that combines PBA-mediated targeting with Notch-1 pathway inhibition by SUL, the study aims to enhance therapeutic selectivity and efficacy against an aggressive BC subtype, triple negative BC (TNBC), which lacks well-defined molecular targets. Methods The PBA-SUL@SLN formulation was prepared using emulsification-solvent evaporation method and analyzed for the particle size (PS), zeta potential (ZP), entrapment efficiency (EE), and pH sensitive drug release. Cellular uptake studies were conducted to examine selective internalization in TNBC cells. The therapeutic efficacy was assessed by evaluating Notch-1expression modulation of epithelial-to-mesenchymal transition (EMT), cancer stem cell (CSC) activity, and cytotoxic effects in TNBC cell compared to normal cells. Results The PBA-SUL@SLN formulation exhibited an optimal PS of (153.35 nm), a ZP of (22.87 mV), and an EE of 83.06%, with preferential drug release observed in the acidic tumor microenvironment. Increased cellular uptake in MDA-MB-231 cells led to notable downregulation of Notch-1, inhibition of EMT, and potential reduction in CSC activity. Cytotoxicity assays revealed strong and selective efficacy against TNBC cells while causing minimal effects on normal cells. Conclusions The PBA-SUL@SLN formulation presents a promising targeted therapeutic strategy for TNBC, addressing key limitations of existing treatments.

Covalent organic frameworks (COFs) show great potential as drug delivery systems (DDSs) due to their customizable structures, stability, and capacity for pore surface functionalization. However, their natural hydrophobicity limits their dispersion in water, posing challenges for biological applications. We address this issue by initially reducing a COF (Az-COF) to an amine-linked form (Az-AL-COF) and subsequently sulfonating it to obtain Az-AL-SO3H-COF, a water-dispersible derivative. Water contact angle (WCA) analysis confirmed increased hydrophilicity across the series of 84.5, 61.2, and 54.7° for Az-COF, Az-AL-COF, and Az-AL-SO3H-COF, respectively. Using doxorubicin (Dox) as a model drug, the modified COFs exhibited pH-sensitive drug release, with greater release at acidic pH (5.6) compared to neutral pH (7.4). Cytotoxicity assays revealed that Az-AL-SO3H-COF was biocompatible with normal cells (MCF-10) while effectively suppressing the growth of cancer cells (MDA-MB-231). The Dox-loaded sulfonated COF (Dox@Az-AL-SO3H-COF) showed selective cytotoxicity against cancer cells, highlighting its potential as a pH-responsive, biocompatible DDS for cancer treatment.

Conventional treatments for glioblastoma (GBM) are hindered by systemic toxicity, limited blood–brain barrier penetration, and therapeutic resistance. To address these challenges, we developed dual-functionalized gold nanoparticles (AuNPs) conjugated with a biotinylated NFL-TBS.40-63 peptide and the chemotherapeutic agent doxorubicin. This platform integrates targeted delivery and therapeutic action to enhance efficacy while minimising off-target effects. Our findings reveal superior cellular uptake, dose- and time-dependent cytotoxicity, and apoptosis induction in GBM cells compared to mono-functionalized counterparts. Furthermore, pH-sensitive drug release profiles underscore the system’s potential to exploit the tumour microenvironment’s acidic conditions for precise drug delivery. Comprehensive characterisation confirmed the stability, biocompatibility, and functional efficacy of the dual-functionalized AuNPs. This study highlights the promise of these nanoconjugates as a multimodal approach to GBM therapy, paving the way for further translational research in nanomedicine.

Peptide-based therapeutics have gained attention in cancer treatment because of their good specificity, low toxicity, and ability to modulate immune responses. However, challenges such as enzymatic degradation and poor bioavailability limit their clinical application. Peptide-functionalized poly(lactic-co-glycolic acid) (PLGA) systems have emerged as a transformative platform in cancer therapy that offers unique advantages, including enhanced stability, sustained release, and precise delivery of therapeutic agents. This review highlights the synergistic integration of peptides with PLGA and addresses key challenges of peptide-based therapeutics. The application of peptide-functionalized PLGA systems encompasses a diverse range of strategies for cancer therapy. In chemotherapy, peptides disrupt critical tumor pathways, induce apoptosis, and inhibit angiogenesis, demonstrating their versatility in targeting various aspects of tumor progression. In immunotherapy, peptides act as antigens to stimulate robust immune responses or as immune checkpoint inhibitors to restore T cell activity, overcoming tumor immune evasion. These systems also harness the enhanced permeability and retention effect, facilitating preferential accumulation in tumor tissues while leveraging tumor microenvironment (TME)-responsive mechanisms, such as pH-sensitive or enzyme-triggered drug release, to achieve controlled, localized delivery. Collectively, peptide-functionalized PLGA systems represent a promising, versatile approach for precise cancer therapy that integrates innovative delivery strategies with highly specific, potent therapeutic agents.