Journal of Materials Chemistry B最新文献

In this work, an expedite synthesis was developed for a self-assembled micelle carrier for the antimicrobial peptide LL18. Covalent one-pot functionalization of dextrin with succinylated vitamin D3 and succinic anhydride produced an amphiphilic material that undergoes self-assembly into micelles in aqueous medium. Succinylated dextrin–vitamin D3 micelles were efficiently loaded with LL18 by electrostatic and hydrophobic interactions. Remarkably, the LL18-loaded micelle formulation dramatically improves the antibacterial activity of free LL18 against S. aureus, completely abrogates its severe hemolytic activity, redirects the internalization of LL18 from the perinuclear region of osteoblasts to the lysosomes and reduces cellular toxicity towards osteoblasts and macrophages. Overall, this work demonstrates that self-assembled micelle formulations based on dextrin, vitamin D3 and antimicrobial peptides, are promising platforms to develop multifunctional antibiotic-independent antimicrobial agents, not prone to the development of bacterial resistance, to treat bone infections.

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.

Precise navigation within intricate biological systems is pivotal for comprehending cellular functions and diagnosing diseases. Fluorescent molecular probes, designed to target specific biological molecules, are indispensable tools for this endeavor. This paper delves into the revolutionary potential of artificial intelligence (AI) in crafting highly precise and effective fluorescent probes. We will discuss how AI can be employed to: design new subcellular dyes by optimizing physicochemical properties; design prospective subcellular targeting probes based on specific receptors; quantitatively explore the potential chemical laws of fluorescent molecules to optimize the optical properties of fluorescent probes; optimize the comprehensive properties of the probe and guide the construction of multifunctional targeting probes. Additionally, we showcase recent AI-driven advancements in probe development and their successful biomedical applications, while addressing challenges and outlining future directions towards transforming subcellular research, diagnostics, and drug discovery.

A nitric oxide (NO) photodonor (1) capable of releasing two NO molecules through a stepwise mechanism has been covalently grafted to blue-emitting N-doped carbon dots (NCDs). The resulting water-soluble nanoconjugate (NCDs-1), ca. 10 nm in diameter, exhibits a new absorption band not present in the simple physical mixture of the two components and is attributable to strong electronic interactions between them in the ground state. Blue light excitation of NCDs-1 leads to NO photogeneration with an efficiency almost one order of magnitude higher than that observed for 1 alone, probably due to a photoinduced electron transfer between the NCDs and the grafted 1. Photoexcitation of the nanoconjugate also results in effective photothermal conversion, which is negligible in the naked NCDs. Furthermore, in contrast to 1, the nanoconjugate liberates NO also under excitation with green light. Finally, the typical blue fluorescence of the NCDs is quenched in NCDs-1 but restored upon the photouncaging of the second NO molecule, providing readable and real-time information about the amount of NO photogenerated.

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.

Objective. The purpose of this study is to develop, optimize, and evaluate the in vivo effectiveness of orally administered silibinin-loaded nanostructured lipid carriers (SB-NLCs) in amyloid β-induced Alzheimer's disease in Wistar rats. Methods. The emulsification-solvent evaporation method was used for preparing the NLCs, using stearic acid, triacetin, and Cremophor® RH40. The statistical optimization of SB-NLCs was done using the Box–Behnken design (BBD). Then, the following parameters were evaluated: zeta potential, average size, in vitro drug release, and drug entrapment efficiency. Physicochemical properties of the optimized SB-NLCs were determined by FTIR, DSC, and P-XRD. The behavioral (OFT, NOR, MWM), histological (H&E, Congo Red), and biochemical (TAC, MDA, GSH) tests were conducted on 48 male Wistar rats. Results. The findings showed that the mean particle size, zeta potential and entrapment efficiency of optimized SB-NLCs were 194.71 ± 14.06 nm, −12.46 ± 0.25 mV, and 72.13% ± 1.41, respectively. XRD and DSC studies confirmed a reduction in the crystallinity of SB which occurred due to its embedment in the nanostructured lipid. The FTIR results indicated the lack of existence of any chemical interaction between the carrier components and the drug. Drug release in the external environment was slow and steady. Drug-containing nanoparticles showed good stability during three months of storage at 4 °C. The behavioral test of OFT showed no significant change between groups. The group treated with SB-NLCs showed a markedly higher discrimination rate compared to the Aβ group (p < 0.001). The time of the SB-NLC treated group in the target area was considerably more than the time of the SB and Aβ groups, respectively (p < 0.01, p < 0.001), in the MWM test. Histological and biochemical analysis revealed better results in the SB-NLC group as against the SB group. Conclusion. SB-NLCs can be considered as a promising formulation for the proper treatment of Alzheimer's disease in the oral drug delivery system.

Musculoskeletal disorders are on the rise, and despite advances in alternative materials, treatment for orthopedic conditions still heavily relies on biometal-based implants and scaffolds due to their strength, durability, and biocompatibility in load-bearing applications. Bare metallic implants have been under scrutiny since their introduction, primarily due to their bioinert nature, which results in poor cell–material interaction. This challenge is further intensified by mechanical mismatches that accelerate failure, tribocorrosion-induced material degradation, and bacterial colonization, all contributing to long-term implant failure and posing a significant burden on patient populations. Recent efforts to improve orthopedic medical devices focus on surface engineering strategies that enhance the interaction between cells and materials, creating a biomimetic microenvironment and extending the service life of these implants. This review compiles various physical, chemical, and biological surface engineering approaches currently under research, providing insights into their potential and the challenges associated with their adoption from bench to bedside. Significant emphasis is placed on exploring the future of bioactive coatings, particularly the development of smart coatings like self-healing and drug-eluting coatings, the immunomodulatory effects of functional coatings and biomimetic surfaces to tackle secondary infections, representing the forefront of biomedical surface engineering. The article provides the reader with an overview of the engineering approaches to surface modification of metallic implants, covering both clinical and research perspectives and discussing limitations and future scope.

A need to enhance the precision and specificity of therapeutic nanocarriers inspires the development of advanced nanomaterials capable of sensing and responding to disease-related cues. Self-assembled peptides offer a promising nanocarrier platform with versatile use to create precisely defined nanoscale materials. Disease-relevant cues can range from large biomolecules, such as enzymes, to ubiquitous small molecules with varying concentrations in healthy versus diseased states. Notably, pH changes (i.e., H⁺ concentration), redox species (e.g., H₂O₂), and glucose levels are significant spatial and/or temporal indicators of therapeutic need. Self-assembled peptides respond to these cues by altering their solubility, modulating electrostatic interactions, or facilitating chemical transformations through dynamic or labile bonds. This review explores the design and construction of therapeutic nanocarriers using self-assembled peptides, focusing on how peptide sequence engineering along with the inclusion of non-peptidic components can link the assembly state of these nanocarriers to the presence of disease-relevant small molecules.

Light-activated fluorescence represents a potent tool for investigating subcellular structures and dynamics, offering enhanced control over the temporal and spatial aspects of the fluorescence signal. While alkyl-substituted tetrazine has previously been reported as a photo-trigger for various fluorophore scaffolds, its limited photochemical efficiency and high activation energy have constrained its widespread application at the biomolecular level. In this study, we demonstrate that a single sulfur atom substitution of tetrazine greatly enhances the photochemical properties of tetrazine conjugates and significantly improves their photocleavage efficiency. Notably, the resulting sulfur–tetrazine can be activated using a lower-energy light source, thus transforming it into a valuable visible-light photo-trigger. To introduce this photo-trigger into biological systems, we have developed a series of visible-light activatable small molecular dyes, along with a photoactivatable noncanonical amino acid containing sulfur–tetrazine. Using the Genetic Code Expansion technology, this novel amino acid is genetically incorporated into fluorescent protein molecules, serving as a phototrigger to create an innovative photoactivatable protein. These advancements in tetrazine-scaffold photo-trigger design open up new avenues for generating photoactivatable biomolecules, promising to greatly facilitate the exploration of biological functions and structures.

Stimuli-responsive nanoscale polymer–drug conjugates are one of the most promising alternatives in the realm of advanced therapeutics, rendering several characteristics such as spatio-temporal control over drug release, reduced off-target toxicity, enhanced bioavailability, and longer blood circulation time of the drug. Fostered by the aforementioned conceptualization, our quest to develop an ideal polymer–drug conjugate has originated the present investigation of developing a reactive oxygen species (ROS) and esterase-responsive self-assembled polymer–drug (chlorambucil, CBL) conjugate with biotin pendants (DP2) for cancer cell targeting, surrogating another antineoplastic drug, doxorubicin (DOX) via physical encapsulation (DP2@DOX). The ROS and esterase trigger not only released the covalently stitched CBL but also resulted in DOX release by dismantling the amphiphilic balance of the nanoaggregates. Biotinylation-mediated enhancement of cellular uptake of DP2@DOX was reflected in the synergistic anticancer activity of both the drugs (CBL and DOX) in HeLa cells (biotin receptor-positive cells) compared to HEK 293T cells (biotin receptor-negative cells). Furthermore, the selective internalization of the fluorophore-tagged DOX-loaded polymer (DP4@DOX) in HeLa cells compared to HEK 293T cells was confirmed by confocal microscopy and flow cytometry. In summary, the present investigation demonstrates a state-of-the-art self-assembled polymer–drug conjugate as a next-generation dual stimuli-responsive drug delivery vehicle.