Search Results (593)

The rational design of multifunctional drug delivery systems capable of achieving precise drug release remains a huge challenge. Herein, we designed a stimuli-responsive dendritic-DNA-based nanohydrogel as a nanocarrier to achieve the co-delivery of doxorubicin and HMGN5 mRNA-targeting antisense oligonucleotides, thus achieving dual therapeutic effects. The nanocarrier, constructed from dendritic DNA with three crosslinking branches and one loading branch, formed biocompatible and programmable DNA nanohydrogels. The C-rich sequences in the crosslinking branches conferred pH sensitivity, while the loading strand enabled efficient incorporation of a shielding DNA/ASO complex. DOX encapsulation yielded a chemo–gene co-delivery platform. Upon cellular uptake by cancer cells, the nanocarrier disassembled in the acidic tumor microenvironment, releasing DOX for chemotherapy and ASOs via toehold-mediated strand displacement (TMSD) for targeted gene silencing. Cellular studies demonstrated significantly enhanced cancer cell inhibition compared to single-agent treatments, highlighting strong combined effects. This study provides a novel strategy for tumor-microenvironment-responsive co-delivery, enabling precise, on-demand release of therapeutic agents to enhance combined chemo–gene therapy. Full article

Mercury is naturally present in soils at trace concentrations, but its cycle is increasingly disrupted by anthropogenic activities, which affect its distribution and behavior. Due to its toxic nature, mercury has become a significant focus in environmental and public health policies. Following the detection of mercury anomalies during groundwater quality monitoring at the Pays de Caux study site (France), a comprehensive multidisciplinary research effort was initiated. This included geological and hydrogeological studies aimed at tracking mercury concentrations in piezometric wells and identifying the sources of these anomalies. This study seeks to assess the groundwater quality and characteristics from ten hydrogeological wells. The evaluation will focus on key hydrogeological parameters, including pH, redox potential (Eh), suspended solids, and groundwater levels, as well as a detailed geochemical analysis of elements such as Hg, Fe, Mn, Zn, Pb, and Cu. The mobilization of mercury and other metallic traces elements is strongly governed by environmental factors. Hydrochemical analyses highlight the complex interplay of various parameters that influence the chemical forms and behavior of mercury in both soil and groundwater. The results from the piezometric measurement campaigns (Pz1 to Pz7) have provided crucial insights, enabling the development of hypotheses about mercury’s behavior in the chalk aquifer. It is hypothesized that impermeable areas may trap groundwater for extended periods, leading to the accumulation and abnormal concentration of mercury. This could cause mercury to be intermittently released, potentially affecting the surrounding environment. Mercury concentrations in groundwater are highly sensitive to pH and redox potential (Eh), with low pH and reducing conditions promoting mercury mobilization and the formation of toxic methylated species. The study suggests the chalk aquifer is generally in equilibrium with mercury, but fluctuations in mercury levels between Pz7 and Pz4 are likely due to the heterogeneity of the clay and geological factors such as mineral composition and fracturing. This research provides insights into mercury transfer in heterogeneous environments and emphasizes the need for continuous hydrogeological monitoring, including piezometer readings, to manage mercury dispersion in the aquifer. Full article

Nanomaterials have revolutionized various biological applications, including cosmeceuticals, enabling the development of smart nanocarriers for enhanced skin delivery. This review focuses on the role of nanotechnologies in skincare and treatments, providing a concise overview of smart nanocarriers, including thermo-, pH-, and multi-stimuli-sensitive systems, focusing on their design, fabrication, and applications in cosmeceuticals. These nanocarriers offer controlled release of active ingredients, addressing challenges like poor skin penetration and ingredient instability. This work discusses the unique properties and advantages of various nanocarrier types, highlighting their potential in addressing diverse skin concerns. Furthermore, we address the critical aspect of biocompatibility, examining potential health risks associated with nanomaterials. Finally, this review highlights current challenges, including the precise control of drug release, scalability, and the transition from in vitro to in vivo applications. We also discuss future perspectives such as the integration of digital technologies and artificial intelligence for personalized skincare to further advance the technology of smart nanocarriers in cosmeceuticals. Full article

Stroke remains a leading cause of disability worldwide, underscoring the urgent need for novel and innovative therapeutic strategies to enhance neuroprotection, support regeneration, and improve functional recovery. Previous research has shown that phytochemicals such as curcumin, tannic acid, gallic acid, ginsenosides, resveratrol, and isorhamnetin display extensive neuroprotective properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. These natural compounds could also promote neurogenesis, angiogenesis, and the preservation of the blood–brain barrier. Despite their promising bioactivities, clinical application is often limited by poor solubility, bioavailability, and suboptimal pharmacokinetics. Hydrogels offer a promising solution by encapsulating and controlling the gradual release of these phytochemicals directly at the site of injury. Recent advancements in hydrogel formulations, constructed from biopolymers and functionalized using nanotechnological approaches, could significantly improve the solubility, stability, and targeted delivery of phytochemicals. Controlled release profiles from pH-sensitive and environment-responsive hydrogels could ensure that the compounds’ therapeutic effects are optimally timed with individual and critical stages of post-stroke repair. Moreover, hydrogel scaffolds with tailored material properties and biocompatibility can create a favorable microenvironment, reducing secondary inflammation, enhancing tissue regeneration, and potentially improving functional and cognitive outcomes following stroke. This review explores the potential of integrating phytochemicals within hydrogel-based delivery systems specifically designed for post-stroke recovery. The design and synthesis of biocompatible, biodegradable hydrogels functionalized especially with phytochemicals and their applications are also discussed. Lastly, we emphasize the need for additional robust and translatable preclinical studies. Full article

Gaseous chlorine dioxide (ClO₂) is a potent antimicrobial agent used to control microbial contamination in food and water. This study evaluates the bactericidal activity of gaseous ClO₂ released from a sodium chlorite (NaClO₂) pad against Campylobacter jejuni. Exposure to a low concentration (0.4 mg/L) of dissolved ClO₂ for 2 h resulted in a >93% reduction of C. jejuni, highlighting the bacterium’s extreme sensitivity to gaseous ClO₂. To elucidate the molecular mechanism of ClO₂-induced bactericidal action, transcriptomic analysis was conducted using RNA sequencing (RNA-seq). The results indicate that C. jejuni responds to ClO₂-induced oxidative stress by upregulating genes involved in reactive oxygen species (ROS) detoxification (sodB, ahpC, katA, msrP, and trxB), iron transport (ceuBCD, cfbpABC, and chuBCD), phosphate transport (pstSCAB), and DNA repair (rdgB and mutY). Reverse transcription-quantitative PCR (RT-qPCR) validated the increased expression of oxidative stress response genes but not general stress response genes (spoT, dnaK, and groES). These findings provide insights into the antimicrobial mechanism of ClO₂, demonstrating that oxidative damage to essential cellular components results in bacterial cell death. Full article

In this study, novel fluorescent DNA biosensors for mercury (Hg²⁺) and silver (Ag⁺) ions were developed based on thymine (T)- and cytosine (C)-rich recognition elements in combination with exonuclease III and a mismatch-catalyzed hairpin assembly (MCHA)-based cascade isothermal signal-amplification strategy. In the presence of the respective target analytes, the recognition element terminals form so-called T-Hg²⁺-T or C-Ag⁺-C structures, resulting in cleavage by Exo III and the release of the trigger strand for MCHA. This binds to the H1 hairpin, which is fluorescently labeled with carboxyfluorescein (FAM) and tetramethylrhodamine (TAMRA), disrupting fluorescence resonance energy transfer between them and, thus, restoring FAM fluorescence, generating a strong signal at 520 nm. The linear range of the Hg²⁺ sensor is 0.5 to 3 pM, with a detection limit of 0.07 pM. The recovery range in actual spiked water samples is between 98.5% and 105.2%, with a relative standard deviation (RSD) ranging from 2.0% to 4.2%. The linear range of the Ag⁺ sensor is 10 to 90 pM, with a detection limit of 7.6 pM. The recovery range in actual spiked water samples is between 96.2% and 104.1%, with an RSD ranging from 3.2% to 6.3%. The cascade isothermal signal amplification strategy effectively enhances sensor sensitivity, while MCHA decreases the false-positive rate. The aptamer sensor exhibits high specificity, is resistant to interference, and can be used for the detection of Hg²⁺ and Ag⁺ in environmental water samples. Full article

Drug-loaded hydrogels are promising for modern medicine due to their physical modifiability. However, most hydrogels suffer from poor swelling, which limits their drug encapsulation and release capabilities. In this study, Poly (N-(2-hydroxyethyl) acrylamide-co-acrylic acid) (Poly (HEAA-co-AA)) hydrogels with high swelling properties are synthesized via free radical polymerization of neutralized acrylic monomers. The effects of the material ratio and acrylic acid neutralization degree on the swelling properties of hydrogels in water are investigated, and the swelling properties of hydrogels prepared with different monomer ratios in different pH buffer solutions are systematically studied. The results show that the swelling degree is sensitive to the monomer ratio and pH. The maximum equilibrium swelling degree of the hydrogels occurs at an HEAA to AA molar ratio of 2:2, with values of 11.36 g g⁻¹ at pH 1.68 and 112.79 g g⁻¹ at pH 9.18. Finally, the mechanical properties of PHA hydrogels under different HEAA/AA molar ratios are investigated, showing that the mechanical properties of PHA improved compared to those of PAA. The mechanical properties of the hydrogels are best and show good stability in rheological tests when the molar ratio of HEAA to AA is 2:2. This work has major potential applications in drug carrier systems. Full article

In this project, a new class of temperature- and pH-sensitive hydrogel consisting of N-isopropyl acrylamide (NIPAM), hydroxyethyl methacrylate (HEMA), and acrylamide (AAm) was prepared via a controlled route through the reversible addition–fragmentation chain-transfer (RAFT) polymerization process. Poly(ethyleneglycol) dimethacrylate (PEG-DMA) was used as a long-chain hydrophilic and biocompatible crosslinking agent. The hydrogel structure was confirmed by different characteristic techniques such as ¹H NMR, FT-IR, and SEC, and the morphology and particle diameters were checked via the scanning electron microscopy (SEM) and dynamic light scattering (DLS) methods. Afterward, the as-prepared hydrogel, poly(NIPAM-co-HEMA-co-AAm), was loaded with doxorubicin (DOX) to be used as a temperature- and pH-triggered delivery carrier. The prepared system released DOX slowly at 37 °C and neutral pH, but increased DOX release significantly at 42 °C and acidic pH. The anti-cancer efficiencies of free DOX, hydrogel, and the DOX–hydrogel conjugate were tested in vitro using human colorectal adenocarcinoma HT-29 cell lines. Cytotoxicity evaluation of free DOX compared with the DOX–hydrogel conjugate revealed that more cancer cells were killed with increasing concentration. Moreover, the DOX-mediated apoptosis and ROS levels showed the beneficial effects of poly(NIPAM-co-HEMA-co-AAm) hydrogel for cancer drug delivery. Generally, the results suggest that this system can be a potential candidate for designing drug delivery systems. Full article

This study focuses on analyzing the in vitro release characteristics, as well as improving the penetration rate and stability of hydrocortisone acetate and pramoxine. This medication combination (hydrocortisone and pramoxine) is the first generic drug product utilized to alleviate minor pain, itching, swelling, and discomfort associated with anorectal conditions such as hemorrhoids. Background/Objectives: The developed novel formulations contain hydrocortisone acetate and pramoxine HCl as active ingredients, at least one solvent, at least one penetrating agent, at least one emulsifying agent, at least one surfactant, and at least one antimicrobial preservative, and pH values between 3.0 and 5.0, preferably between 3.5 and 4.5. Methods: Typical semi-solid dosage form quality control tests included appearance, identification, content homogeneity, pH, viscosity, assay, compounds of interest, microbiological testing, and in vitro release testing. In in vitro release testing, a series of formulations containing hydrocortisone acetate and pramoxine were tested for in vitro release across the Strat-M membrane using Franz diffusion cells methodology in comparison to a reference product (Pramosone Cream 2.5%). Results: Quantitative content of the release tests of the active ingredients in the cream, assay tests, antimicrobial preservative efficacy, and stability tests were carried out by high-sensitivity liquid chromatography. Conclusions: In conclusion, the cream formulations developed in this study have the potential to offer more effective treatment compared to reference products in terms of both in vitro release rates, and their reliability and validity were confirmed through validation studies. Full article

Background: Live attenuated bacteria are promising candidates for mucosal vaccine delivery due to their ability to elicit robust immune responses. FimH is the adhesion protein of type 1 fimbriae, which is used as mucosal adjuvants. This study aims to develop a novel attenuated live bacterial vector via fimbriae recovery on Shigella flexneri. Methods: We generated pBAD-Fim/FWL01 by deleting IS elements in the fimbrial cluster of S. flexneri 2a strain T32. Transmission electron microscopy (TEM) and a mannose–sensitive agglutination assay were used to confirm that type 1 fimbriae were displayed on the recombinant strain. We then evaluated the immune induction of pBAD-Fim/FWL01 in J774A.1 murine macrophages and mice. Additionally, we used pBAD-Fim/FWL01 to deliver the neutrophil–activating protein A subunit (NapA) to assess immunogenicity. Results: Functional type 1 fimbriae on pBAD-Fim/FWL01 were confirmed using TEM and mannose–sensitive agglutination assays. Transcriptome analysis, qRT-PCR, and ELISA assays revealed that pBAD-Fim/FWL01 significantly stimulated mouse macrophages to release cytokines IL-1α, IL-1β, IL-6, and IL-10, inducing an immune response. Orally administrated pBAD-Fim-trc-napA-His/FWL01 elicited significant mucosal and humoral immune responses. Conclusions: The strain pBAD-Fim/FWL01, which expresses type 1 fimbriae, holds promise for development as an attenuated bacterial vaccine vehicle. Full article

Nanotechnology, particularly quantum dots (QDs), has ushered in a transformative era in the pharmaceutical and medical industries, offering notable opportunities for nanoscale advancements. These nanoscale particles, known for their exceptional optical properties and quantum confinement, have emerged as indispensable tools in cancer drug delivery and bioimaging. This review delves into various drug conjugation techniques with QDs, including covalent linking, non-covalent conjugation, click chemistry, disulfide linkage, and pH-sensitive linkage. Each method provides distinct advantages, such as enhanced stability, reversibility, specificity, and controlled drug release. Moreover, QDs have demonstrated significant promise in oncology by efficiently delivering drugs to cancerous tissues while minimising systemic toxicity. Investigations into their applications in different cancers, such as blood, brain, cervical, breast cancers, etc., reveal their efficacy in targeted drug delivery, real-time imaging, and improved therapeutic outcomes. However, challenges such as potential toxicity, stability, pharmacokinetics, and targeting specificity must be addressed to fully harness the benefits of QDs in cancer therapy. Future research should focus on developing biocompatible QDs, optimising conjugation techniques, and elucidating their safety profiles and long-term effects in biological systems. Overall, QDs represent a promising frontier in cancer treatment, offering multifaceted capabilities that hold the potential for enhanced therapeutic outcomes and reduced side effects across various cancers. Full article

Mycoplasma pneumoniae (MP) is the main culprit of community-acquired pneumonia. Commonly used laboratory testing methods have many shortcomings. Serological diagnosis has low sensitivity, causing false negatives, while a quantitative real-time polymerase chain reaction (qPCR) requires large equipment and professional staff. To make up for these shortcomings, we proposed a label-free, low-cost, and small-sized ion-sensitive field-effect transistor (ISFET) array based on a low-buffered loop-mediated isothermal amplification (LAMP) assay. A complementary metal oxide semiconductor (CMOS)-based ISFET array with 512 × 512 sensors was used in this system, which responds specifically to H⁺ with a sensitivity of 365.7 mV/pH. For on-chip amplification, a low-buffered LAMP system designed for the conserved sequences of two genes, CARDS and gyrB, was applied. The rapid release of large amounts of H⁺ in the low-buffered LAMP solution led to a speedy increase in electrical signals captured by the ISFET array, eliminating the need for a sophisticated temperature cycling and optical system. The on-chip results showed that the device can accurately complete MP detection with a detection limit of about 10³ copies/mL (approximately 1 copy per reaction). In the final clinical validation, the detection results of eight throat swab samples using the ISFET sensors were fully consistent with the clinical laboratory diagnostic outcomes, confirming the accuracy and reliability of the ISFET sensors for use in clinical settings. And the entire process from sample lysis to result interpretation takes about 60 min. This platform has potential to be used for the point-of-care testing (POCT) of pathogen infections, providing a basis for the timely adjustment of diagnosis and treatment plans. Full article

This study investigates the pH-responsive dissociation mechanism of carbon dot (CD) conjugated with the anticancer peptide proximicin-A (PROXI) using density functional theory (DFT) simulations. The CD@PROXI system, designed for targeted cancer therapy, releases the drug in acidic environments typical of cancer sites. DFT simulations, with the B3LYP-D3BJ functional and 6-311G (d, p) basis set, optimized the conjugate’s geometry under neutral and acidic conditions. The focus was on the pH-sensitive C=N bond, existing in two protonation states. Key parameters evaluated included the HOMO-LUMO gap, bond length, IR spectroscopy, non-covalent interaction (NCI), electron localization function (ELF), density of states (DOSs), and electrostatic potential (ESP). Under neutral pH, the system showed stability with a HOMO-LUMO gap of 3.22 eV, indicating low reactivity. In acidic pH, this gap decreased to 0.40 eV, suggesting higher reactivity and potential for drug release. IR spectroscopy indicated weakened C=N bonds in acidic conditions, with bond length increasing from 1.288 Å to 1.324 Å. NCI analysis revealed increased van der Waals interactions, supporting bond weakening. ELF analysis showed electron localization at reactive sites, while DOS profiles and ESP maps highlighted distinct electronic states and potential dissociation regions in acidic conditions. These findings confirm the potential of CD@PROXI for targeted cancer therapy, with drug release triggered by the acidic tumor microenvironment. Full article

Background: Colorectal cancer (CRC) is one of the common malignant tumors. Chemotherapeutic agents represented by doxorubicin (DOX) are common adjuvant therapies for patients with advanced CRC. However, DOX suffers from dose-dependent cardiotoxicity and myelosuppression due to a lack of targeting and specificity, which severely limits its clinical application. Methods: Herein, we constructed a zeolitic imidazolate framework-8 (ZIF-8) modified by a novel peptide (LT peptide) to deliver the chemotherapeutic drug doxorubicin (DOX) for the targeted treatment of CRC. Results: In this study, LT-PEG@DOX@ZIF-8 nanoparticles were prepared by a simple method with suitable particle size and zeta potential, which were also capable of pH-responsive drug release. In vitro assays exhibited that LT-PEG@DOX@ZIF-8 nanoparticles were effectively taken up by C26 cells, significantly inhibited cell proliferation, and induced apoptosis. Furthermore, in mice models with colorectal tumors, LT-PEG@DOX@ZIF-8 nanoparticles also displayed specific tumor aggregation and exerted anti-tumor effects to prolong the survival of the mice. Conclusions: In conclusion, LT-PEG@DOX@ZIF-8 provides a promising strategy for the delivery of DOX to effectively treat CRC. Full article

Magnetic iron oxide (II,III) nanoparticles (MNPs) are highly interested in biomedicine. However, their application is limited by oxidation, aggregation, rapid clearance from the body, and poor biodistribution. Coating by human serum albumin (HSA), the predominant blood plasma protein, can significantly influence properties, prolong circulation half-life, and enhance tumor capture efficiency. Here, we report the synthesis of oleic acid and Tween20-coated MNPs and their interaction with HSA. The influence of albumin coating on MNP size, zeta potential, aggregation ability, and toxicity was studied. The particles were characterized by dynamic light scattering, transmission electron microscopy, and Fourier transform infrared spectroscopy methods. The nanoparticles’ relaxivities (r₁ and r₂) were assessed under a magnetic field of 1.88 T to evaluate their performance in MRI applications. The anticancer drug doxorubicin (DOX) loading capacity of up to 725 µg/mg for albumin-coated MNPs was determined. DOX-loaded MNPs displayed pH-sensitive drug release during acidic conditions. The series of DOX-loaded nanocomposites indicated inhibition of A549 cell lines, and the IC₅₀ values were evaluated. This research underscores the utility of HSA-coated MNPs in enhancing the efficacy and stability of drug delivery systems in biomedicine. Full article