ACS Applied Bio Materials最新文献

The development of stimuli-responsive drug delivery systems enables targeted delivery and environment-controlled drug release, thereby minimizing off-target effects and systemic toxicity. We prepared and studied tailor-made dual-responsive systems (thermo- and pH-) based on synthetic diblock copolymers consisting of a fully hydrophilic block of poly[N-(1,3-dihydroxypropyl)methacrylamide] (poly(DHPMA)) and a thermoresponsive block of poly[N-(2,2-dimethyl-1,3-dioxan-5-yl)methacrylamide] (poly(DHPMA-acetal)) as drug delivery and smart stimuli-responsive materials. The copolymers were designed for eventual medical application to be fully soluble in aqueous solutions at 25 °C. However, they form well-defined nanoparticles with hydrodynamic diameters of 50-800 nm when heated above the transition temperature of 27-31 °C. This temperature range is carefully tailored to align with the human body's physiological conditions. The formation of the nanoparticles and their subsequent decomposition was studied using dynamic light scattering (DLS), transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and nuclear magnetic resonance (NMR). ¹H NMR studies confirmed that after approximately 20 h of incubation at pH 5, which closely mimics tumor microenvironment, approximately 40% of the acetal groups were hydrolyzed, and the thermoresponsive behavior of the copolymers was lost. This smart polymer response led to disintegration of the supramolecular structures, possibly releasing the therapeutic cargo. By tuning the transition temperature to the values relevant for medical applications, we ensure precise and effective drug release. In addition, our systems did not exhibit any cytotoxicity against any of the three cell lines. Our findings underscore the immense potential of these nanoparticles as eventual advanced drug delivery systems, especially for cancer therapy.

Multielemental transition metal compounds represent a class of promising candidates for the biomedical field due to their unique structure and biomedical application potential. However, their synthesis process remains challenging, which was subject to the high-temperature treatment of the multimetallic elements integrated within one system. Herein, for the first time, we have fabricated the nanotripod, i.e., (FeCoNiCuZnAl)O_x (denoted as HEO) agent, via the structural topotactic transformation of layered double hydroxide (LDH) precursors with the tunable disorder degree, for highly efficient high-entropydynamic therapy associated with metabolism homeostasis. By virtue of this unique high-entropy structure, the outburst reactive oxygen species (ROS) generation can be regulated via turbulence. These unique high-entropy oxides not only presented outstanding ROS generation efficiency but also broke the intracellular metabolic balance cycle (NADH/NAD⁺) by NO_x-like activity, which can disturb the tumor energy metabolism homeostasis, leading to cell apoptosis. Furthermore, in vitro and in vivo experiments both indicate that this agent was a satisfying candidate for magnetic resonance imaging (MRI)-guided therapy. The findings offer a strategy for the development of high-entropydynamic therapy.

Inspired by the intricate cellular morphology and the discoid shape of red blood cells (RBCs), biomimetic tricompartmental microcarriers (TCM) with controlled release profiles were engineered using an electrohydrodynamic-co-jetting technique for efficient management of Parkinson's disease (PD). While jetting, Levodopa (LD), CD (Carbidopa), and ENT (Entacapone) (3 PD drugs) were directly encapsulated in the three individual compartments of the TCM used for oral administration. The optimal shape and controlled release profiles were obtained by employing the Taguchi orthogonal L9 design-of-experiment approach by systematically varying the processing parameters, i.e., solvent ratio, polymer concentration, and flow rate. The "smaller-the-better" norm for the S/N ratio demonstrated the solvent ratio (DMF content) and polymer concentration as the most influential parameters in ensuring the RBC shape and controlling the release of drugs. Analysis of variance and response surface methodology approach provided insights into the optimal influence of control factors on the response variables. Confirmation experiments further validated the optimized microparticles (P_optimized), demonstrating an error of only ∼0.13% in aspect ratio deviation (AR_DEV) and ∼19% (within the tolerance limit) in release factor (RF) from the predicted experiment. Moreover, P_optimized exhibits ∼100% encapsulation efficiency of all three PD drugs, with the cumulative release of ∼100% LD, ∼97% CD, and ∼65% ENT within 5 h of the in vitro study. In addition, in vivo studies such as pharmacokinetics (using healthy rats) and pharmacodynamics [using the MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-injected PD-induced mice model] showed that the TCM can effectively control the release of LD (primary drug) for a prolonged period, thereby promising sustained drug delivery and improved therapeutics outcomes.

Cyanogenic glycosides are plant-derived, nitrogen-containing secondary metabolites that release toxic cyanide ions upon hydrolysis by glycosidic enzymes. Therefore, consuming food items enriched with such compounds without proper remediation can cause acute cyanide intoxication. Thus, in this work, we utilize cyanide-responsive oxidized bisindole-based chromogenic probes to detect cyanogenic glycosides, such as amygdalin and linamarin (LOD: 0.12 μM), in phospholipid membranes. The bilayer surface, owing to its distinct microenvironment, enhances both the sensitivity and specificity of the probes toward amygdalin. The chromogenic response (red to yellow) is influenced by the nature of the lipid membrane (order, polarity, and interfacial hydration) as well as the number of bis-indolyl units in the probe molecules. Semiquantitative analysis of food samples before and after cooking revealed that soaking in water at room temperature significantly reduces the cyanogenic glycoside content. The ability to directly detect cyanogenic glycosides in food samples without pretreatment is a notable aspect of this investigation.

The present study aims to formulate a stimuli-responsive in situ hydrogel system to codeliver acacia honey and glycyrrhizic acid for topical application that will aid in absorbing wound exudates, control microbial infestation, and produce angiogenic and antioxidant effects to accelerate wound healing. Therefore, both the natural active constituents were incorporated within an in situ hydrogel composed of poloxamer and hydroxypropyl methylcellulose (HPMC), where the concentrations of the polymers were optimized using Design-Expert software considering optimum values of the dependent variables, gelation temperature (34-37 °C), gelation time (<10 min), and the viscosity (2000-3500 cPs). The optimized formulation showed improved physicochemical properties such as mucoadhesiveness, porosity, swelling, and spreadability, which makes it suitable for wound application. Additionally, the in situ hydrogel exhibited potent in vitro and ex vivo antioxidant effects, in vitro antimicrobial activities, and ex ovo angiogenic effects. Furthermore, the optimized formulation was found to be nontoxic while tested in the HaCaT cell line and acute dermal irritation and corrosion study. The findings of the in vivo wound-healing studies in experimental animal models showed complete wound closure within 15 days of treatment and accelerated development of the extracellular matrix. In addition, the antioxidant, antimicrobial, angiogenic, and wound-healing properties of acacia honey and glycyrrhizic acid coloaded in situ hydrogel were also found to be promising when compared to the standard treatments. Overall, it can be concluded that the optimized stimuli-responsive in situ hydrogel containing two natural compounds could be an alternative to existing topical formulations for acute wounds.

Dye-contaminated wastewater poses serious environmental risks to ecosystems and human health. Diatoms, algae with nanoporous frustules (cell walls), offer promising potential for wastewater remediation due to their high surface area and adsorption properties. While dead diatom biomass is well-studied for biosorption, research on living diatoms' bioaccumulation and biotransformation potential is limited, with gaps in kinetic and equilibrium modeling of dye adsorption. Here, we analyzed the adsorption of crystal violet (CV) dye onto living Phaeodactylum tricornutum (P-cell) and Navicula cryptocephala var. veneta (N-cell) diatoms by characterizing the physiochemical properties of the species' outer surfaces and monitoring the adsorption of CV using surface-specific second harmonic scattering (SHS) spectroscopy. Direct monitoring of dye adsorption, rather than its removal from the solution, enables a more accurate investigation of adsorption kinetics and thermodynamics, revealing strong correlations with the cell surface structure and composition. We found that the N-cell has a greater adsorption capacity for CV than the P-cell, though with slightly less favorable adsorption free energy. Ionic strength could impact uptake capacities, likely due to competition between metal cations and the dye cation as well as surface screening. SHS experiments revealed a simple adsorption process for N-cells, while P-cells exhibited a multistep process involving CV transport through thinner, nonporous cell walls to the plasmic membrane, contributing to favorable adsorption free energy. The thicker, porous walls of N-cells provided more surface sites, increasing the capacity, while P-cells facilitated deeper uptake. Ionic strength had only a significant effect on adsorption capacity, not adsorption free energy, reflecting the intricacies that govern adsorption and uptake by living organisms. The comprehensive analysis presented herein demonstrates great potential for diatoms to be used as biosorbents in dye remediation and provides systematic relationships between the structure and function of diatom cell walls, which will inform the use of tailored species for more efficient remediation.

Peptide building blocks have been recently proposed for the fabrication of supramolecular nanostructures able to encapsulate and in vivo deliver drugs of a different nature. The primary sequence design is essential for nanostructure property modulation, directing and affecting affinity for specific drugs. For instance, the presence of positively charged residues of lysine (K) or arginine (R) could allow improving electrostatic interactions and, in turn, the encapsulation of negatively charged active pharmaceutical ingredients, including nucleic acids. In this context, here, we describe the formulation and the multiscale structural characterization of hybrid cationic peptide containing hydrogels (HGs). In these matrices, the well-known low-molecular-weight hydrogelator, Fmoc-diphenylalanine (Fmoc-FF, Fmoc = fluorenyl methoxycarbonyl), was mixed with a library of cationic amphiphilic peptides (CAPs) differing for their alkyl chain (from C8 to C18) in a 1/1 mol/mol ratio. The structural characterization highlighted that in mixed HGs, the aggregation is guided by Fmoc-FF, whereas the cationic peptides are only partially immobilized into the hydrogelated matrix. Moreover, morphology, stiffness, topography, and toxicity are significantly affected by the length of the alkyl chain. The capability of the hydrogels to encapsulate negative drugs was evaluated using the 5-carboxyfluorescein (5-FAM) dye as a model.

Although porous frameworks are structurally ideal for the development of biomaterials through drug adsorption, sequestration, and delivery, integration of multiple biofunctions into a biocompatible porous framework would greatly improve its potential for preclinical investigations by increasing both therapeutic value and research and development efficiency. Herein, we report the preparation of a highly biocompatible supramolecular organic framework from an imidazolium-derived tetrahedral monomer and cucurbit[8]uril. The supramolecular organic framework has been revealed to have regular intrinsic porosity and adsorb doxorubicin, photofrin, and heparins driven by hydrophobicity and/or ion-pairing electrostatic interactions. In vivo or in vitro assays illustrate that this adsorption leads to efficient intracellular delivery of doxorubicin, which enhances its antitumor efficacy, elimination of photofrin, which inhibits its post-treatment phototoxicity without reducing its photodynamic therapeutic activity, and sequestration of (low-molecular-weight) heparins, which neutralizes their anticoagulation activity more efficiently than clinically used protamine.

Ru(bpy)₃²⁺ is commonly used in electrochemiluminescence (ECL) as a conventional luminophore. However, Ru(bpy)₃²⁺ can leak off the electrode surface, resulting in a reduced ECL signal. In this work, a nanocube composite material Ru@ZIF was prepared by incorporating doping luminescent Ru(bpy)₃²⁺ into the skeleton of Zn(II) ions and 2-methylimidazole (2-MI), and the ECL probe Ru@ZIF-Pd was prepared by in situ growth of Pd nanoparticles (Pd NPs). Potassium persulfate (K₂S₂O₈) was used as a coreactant to investigate the cathodic ECL behavior. The ZnCoCH@MXene-Au (ZC@T-Au) was used as a coreactant accelerator to promote the production of SO₄^•-, which effectively amplified the ECL intensity of Ru@ZIF-Pd. Under optimal experimental conditions, we successfully constructed an aptamer ECL sensor, which achieves an accurate detection of acetamiprid from 0.1 fM to 10 μM with a detection limit of 0.029 fM. It provides a potential idea for the detection of pesticide residues in food.