Journal of materials chemistry. B最新文献

In this report, a functionalized hydroxyphenyl benzothiazole (HBT) derivative has been synthesized and anchored onto the perylene diimide (PDI) core at the -bay position (PHI). PHI has been explored for the generation of radical anions (PH1˙-) and dianions (PH12-) in 20% HEPES buffer-DMSO solution using H₂S as a sacrificial electron donor. The PH1˙- has a half-life (t_1/2) of 1.5 h and 3 h in oxygenated and hypoxic conditions, respectively. The formation of radical anions has been confirmed by optical (absorbance and fluorescence) methods, cyclic voltammetry (CV), differential pulse voltammetry (DPV), and femtosecond transient absorbance spectroscopy along with current-voltage (I-V) and NOBF₄ studies. The PH1˙- showed peroxidase-like activity for the reduction of H₂O₂ as low as 170 fmol L^-1 (fM) giving a colour change from sea green to pink. The biochemical assay which consists of PH1˙-+ GOx has been further utilized as a glucose sensor. Upon addition of glucose (0-8 nM) in the biochemical assay, the in-situ produced H₂O₂ (after oxidation of glucose with GOx) oxidized PH1˙- to PH1 giving a sea green to pink colorimetric read out along with a decrease in the absorption intensities at 720, 815, 880 and 950 nm and the emergence of absorption intensity at 541 nm. The lowest limit of detection is 85 fM. We also explored this biochemical assay for the detection of 860 fM of glucose in a 10% blood serum. Similarly, fluorometric, CV and DPV studies were carried out for the detection of glucose using this biochemical assay. The smartphone-assisted RGB colour analyser showed large variations in the red colour and this RGB based colour differentiation can be used for the detection of 1 nM of glucose.

Antimicrobial-resistant bacteria pose a significant threat to humans, prompting extensive research into developing new antimicrobial peptides (AMPs). The biomembrane is the first barrier of a biological cell, hence, comprehending the interaction and self-assembly of AMPs in and around such membranes is of great importance. In the present study, several biophysical techniques have been applied to explore the self-assembly of ubiquicidin (29-41), an archetypical AMP, in and around the phospholipid monolayers formed at air-water interface. Such a monolayer mimics one of the leaflets of a lipid bilayer. The surface pressure-area isotherm exhibits the strongest interaction with a negatively charged lipid, 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DPPG). The weakest affinity was towards the zwitterionic lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Another zwitterionic lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), shows an intermediate affinity. This affinity was quantified by analyzing alterations in the effective mean molecular area of the lipid, the in-plane compressional modulus of the assembly, and the electrostatic potential induced by the presence of peptides. The precise organization of the peptide around the lipid monolayer at a sub-nanometre length scale was revealed using synchrotron-based X-ray reflectivity measurements from the air-water interface. Information about the selective interaction of the peptide with lipids and their varied orientation at the lipid-water interface could be useful in understanding the selectivity of AMP in developing new antibiotics.

Trace detection of bioactive small molecules (BSMs) in body fluids is of great importance for disease diagnosis, drug discovery, and health monitoring. Based on the chiral ligand of 4,4'-(1,2-dihydroxyethane-1,2-diyl)dibenzoic acid (H₂L), an achiral 3D porous Ni(II)-MOF, with a trinuclear cluster based (3,9)-c {4²·6}₃{4⁶·6²¹·8⁹}-xmz net, was constructed under solvothermal conditions. Benefiting from its robust framework and excellent luminescent performance, NiMOF was endowed with remarkable capabilities in efficiently, rapidly, and sensitively detecting the 3-nitrotyrosine (3-NT) biomarker and 6-propyl-2-thiouracil (6-PTU) thyroid drug based on the spectral overlap and photo-induced electron transfer (PET) caused luminescence quenching response. Notably, NiMOF exhibited exceptional performance in quantifying 3-NT and 6-PTU in urine samples, yielding highly satisfactory results. Additionally, an intelligent detection system was crafted to enhance the reliability and practicability of 3-NT/6-PTU detection in urine, based on tandem combinational logic gates. This work not only heralds a promising trajectory in the development of MOF-based luminescent sensors, but also paves the way for the intelligent monitoring of BSMs in real bodily fluids.

Endogenous release of HSO₃^- during the enzymatic oxidation of sulfur containing amino acids in mitochondria or insufficiency of sulfite oxidase results in the accumulation of sulfite and thiosulfate in biological fluids affecting mitochondrial homeostasis of brain mitochondria associated with serious clinical symptoms related to neurological disorders. The red fluorescent probe MGQ undergoes self-assembly in water and reveals aggregation induced quenching of fluorescence. MGQ reveals 143-fold and 179-fold increases in fluorescence intensity at 645 nm, respectively, in the presence of HSA and BSA and does not significantly differentiate between two albumins. The detailed studies of MGQ have been performed in the presence of BSA. The presence of other enzymes/proteins and amino acids, viz. pepsin, trypsin, lysozyme, Bromelain, lysine, histidine, hemoglobin, etc., does not affect the fluorescence of MGQ or MGQ-BSA solutions and points to high selectivity towards BSA. The limit of detection for BSA is 10 nM. In PBS buffer, MGQ in the absence of BSA does not react with HSO₃^- and sluggishly in a 1 : 1 ethanol-water mixture. However, in the confined space of BSA/HSA, MGQ displays a signal amplification, undergoes instantaneous Michael type addition of HSO₃^- and results in a ratiometric change in fluorescence intensity in ≤1.5 min with the decrease of red fluorescence at 645 nm and emergence of green fluorescence at 515 nm. The LOD for the detection of HSO₃^- is 4 nM.

We synthesized an unoxidized bis-indolyl methane (BIM) derivative (probe 1) comprising of tetraphenylethylene (TPE) as the signalling moiety. The amphiphilic probe could form self-assembled nanoscopic aggregates in the aqueous medium. The emission of 1 in non-polar solvents originates from the LE state, while in polar solvents, it is dominated by TICT. Moreover, probe 1 exhibited a 'turn-on' fluorescence response for both uric acid (with a blue shift in emission maxima) and phytic acid (with a red shift in emission maxima). Therefore, the present system provides an exceptional opportunity to distinguish between phytic acid and uric acid by considering two different emission channels. Mechanistic investigations revealed that both H-bonding and electrostatic interactions between the probe and analytes could effectively cause restricted intramolecular rotations, leading to a turn-on response. Additionally, in the case of phytic acid, larger aggregates were observed with prominent CT characteristics. The change in the extent of charge transfer interaction in the formed adducts resulted in distinct fluorescence responses with phytic acid and uric acid. Furthermore, we explored the applicability of the present system in the screening of real-life samples, such as uric acid in urine samples and phytic acid in grains. The LOD for phytic acid and uric acid was found to be ∼5.48 nM and 10.4 nM, respectively. The quantitative nature of the system was confirmed, showing promising results in terms of recovery values (between 95.6% and 104.2%) and detection limits. Additionally, we also employed handy paper strips for the on-site monitoring of phytic acid and uric acid, thereby eliminating the need for complex instrumentation or trained technicians.

Nanoparticles (NPs) derived from branched copolymers of poly (β-L-malic acid) (PMLA) have been extensively investigated for drug delivery due to their high density of pendant carboxyl groups. This abundant functional group availability enhances their potential as effective drug delivery systems; however, the strong negative charge of PMLA poses a challenge in its uptake by cancer cells due to electrostatic repulsion. In this study, we developed novel enzyme- and pH-sensitive nanoparticles (EP-NPs) based on PMLA, demonstrating tumor-specific behavior and selective activation within tumor tissues. To enhance the cellular internalization of the nanoparticles, we incorporated transactivator of transcription (TAT). In summary, long-chain polyethylene glycol (PEG) was conjugated to PMLA to confer specificity to the TAT peptide. This was achieved using a tetrapeptide linker: alanine-alanine-asparagine-leucine (AANL), which serves as a substrate for legumain. Legumain is a highly conserved cysteine protease primarily found in lysosomes and blood vessels, initially discovered in legumes. It is markedly overexpressed in numerous solid tumors, as well as in endothelial cells and tumor-associated macrophages. The release of doxorubicin in tumor cells was sustained due to the low pH (5.0-5.5) and degradation of PMLA. The PEG modification optimized the particle size and shielded the nanoparticles from plasma proteins and detection by the reticuloendothelial system, thereby prolonging their long circulation time. Once the nanoparticles reached the tumor microenvironment, the AANL was cleaved by legumain, exposing the TAT peptide on the surface, which enhances cellular internalization. Both in vitro and in vivo efficacy studies demonstrated that these EP-NPs significantly inhibited tumor growth while exhibiting negligible systemic toxicity, thereby suggesting that the developed enzyme/pH-sensitive PMLA-based nanoparticle holds great promise as an anti-tumor drug delivery system.

Quantification of hydroxyl radicals (˙OH), one form of reactive oxygen species (ROS), plays critical roles in early diagnosis and treatment monitoring of various diseases. In this work, we report the development of a responsive nanoprobe for ratiometric fluorescence detection and imaging of ˙OH in macrophage polarization. The nanoprobe, BSA-CCA@LDH-SRB, was designed and prepared using coumarin 3-carboxylic acid (CCA) as the sensing unit for ˙OH, and sulforhodamine B (SRB) loaded on layered double hydroxide (LDH) served as the fluorescent reference component. The coupling of CCA to bovine serum albumin (BSA) and the loading of BSA-CCA on the surface of LDH enabled the nanoprobe for fluorescence detection of ˙OH with high sensitivity and minimal interference from other biomolecules, ions, and ROS. The emission of the prepared BSA-CCA@LDH-SRB at 444 nm emerged and the intensity was increased according to the concentration of ˙OH, while the emission at 580 nm was maintained, allowing the nanoprobe for ratiometric fluorescence (F_444/580) detection of ˙OH. Loading of the BSA protein on the LDH surface and the biocompatibility and colloidal stability of the LDH-based fluorescent nanoprobe were further improved, facilitating the detection of ˙OH generation in macrophage polarization stimulated by both biomolecules and physical ultrasound irradiation. This study thus offers a new nanoprobe as the tool for investigating ˙OH evolutions, advancing the biomedical investigations of macrophage polarization associated inflammation.

Melanoma is one of the most significant and dangerous superficial skin tumors with a high fatality rate, thanks to its high invasion rate, drug resistance and frequent metastasis properties. Unfortunately, researchers for decades have demonstrated that the outcome of using conventional therapies like chemotherapy and immunotherapy with normal drug delivery routes, such as an oral route to treat melanoma was not satisfactory. The severe adverse effects, slow drug delivery efficiency and low drug accumulation at targeted malignancy sites all lead to poor anti-cancer efficacy and terrible treatment experience. As a novel transdermal drug delivery system, microneedles (MNs) have emerged as an effective solution to help improve the low cure rate of melanoma. The excellent characteristics of MNs make it easy to penetrate the stratum corneum (SC) and then locally deliver the drug towards the lesion without drug leakage to mitigate the occurrence of side effects and increase the drug accumulation. Therefore, loading chemotherapeutic drugs or immunotherapy drugs in MNs can address the problems mentioned above, and MNs play a crucial role in improving the curative effect of conventional treatment methods. Notably, novel tumor therapies like photothermal therapy (PTT), photodynamic therapy (PDT) and chemodynamic therapy (CDT) have shown good application prospects in the treatment of melanoma, and MNs provide a valid platform for the combination of conventional therapies and novel therapies by encompassing different therapeutic materials in the matrix of MNs. The synergistic effect of multiple therapies can enhance the therapeutic efficacy compared to single therapies, showing great potential in melanoma treatment. Dissolving MNs have been the most commonly used microneedles in the treatment of melanoma in recent years, mainly because of their simple fabrication procedure and enough drug loading. So, considering the increasing use of dissolving MNs, this review collects research studies published in the last four years (2020-2024) that have rarely been included in other reviews to update the progress of applications of dissolving MNs in anti-melanoma treatment, especially in synergistic therapies. This review also presents current design and fabrication methods of dissolving MNs; the limitations of microneedle technology in the treatment of melanoma are comprehensively discussed. This review can provide valuable guidance for their future development.

Oral cancer is a significant global health challenge, with conventional treatments often resulting in substantial side effects and limited effectiveness. Phototherapy, encompassing photodynamic and photothermal therapy, presents a promising alternative by selectively targeting and destroying cancer cells with minimal systemic toxicity. However, issues such as insufficient light penetration and limited tumor specificity have restricted their clinical use. Recent advancements in nanosystems have addressed these challenges by enhancing the solubility, stability, and tumor-targeting capabilities of phototherapy agents. This review delves into the latest advancements in phototherapeutic nanosystems for oral cancer, focusing on the design of innovative nanoformulations and targeted delivery strategies. Additionally, it summarizes recent approaches to enhance the efficacy of photodynamic therapy for oral cancer and examines phototherapy-based combination treatments. These advancements hold the promise of significantly improving treatment outcomes while minimizing side effects in oral cancer therapy.

Oral cancer is one of the leading cancer types, which is frequently diagnosed at an advanced stage, giving patients a poor prognosis and fewer therapeutic choices. To address this gap, exploiting biosensors utilizing anti-biofouling hydrogels for early-stage oral cancer detection in non-invasive body fluids is gaining utter importance. Herein, we have demonstrated the fabrication of an innovative electrochemical immunosensor for the rapid, label-free, non-invasive, and affordable detection of tumor necrosis factor-α (TNF-α), a biomarker associated with oral cancer progression in artificial saliva samples. The gold screen-printed electrodes (gSPEs) are modified with a green synthesized porous and electroactive reduced graphene oxide (rGO) hydrogel utilizing L-cystine (L-cys) as both in situ reducing and surface functionalization agent, followed by covalent immobilization of anti-TNF-α and blocking of residual sites with bovine serum albumin (BSA) to fabricate the BSA/anti-TNF-α/L-cys_rGO hydrogel/gSPE immunosensing platform. The fabricated platform demonstrates excellent performance, with a low limit of detection of 1.20 pg mL^-1, a broad linear range from 1 to 200 pg mL^-1, and a high sensitivity of 2.10 μA pg^-1 mL cm^-2 carried out with differential pulse voltammetry (DPV) technique. Moreover, it exhibits specificity towards TNF-α, even in the presence of potential interferents and other cancer biomarkers. Besides, the biosensor showed good reproducibility and repeatability with a relative standard deviation (%RSD) of 5.11% and 1.85%, respectively. Thus, integrating the L-cys_rGO hydrogel in the immunosensor design offers enhanced performance, paving the way for its application in early-stage oral cancer diagnosis.