Journal of materials chemistry. B最新文献

Treatment of local tumor recurrence and repair of the tissue defects after tumorectomy still remain clinical challenges. Currently, controlled release of therapeutic drugs is one of the widely used approaches to kill the residual and recurrent cancer cells, and stem cell-laden hydrogel scaffolds are promising candidates for soft tissue repair. However, hydrogel scaffolds with the bifunction of controlled release of therapeutic drugs for cancer therapy and loading stem cells for tissue repair are still not well established. In this study, we fabricated a biphasic hydrogel scaffold containing two types of core/shell filaments with drugs and stem cells loaded in the core part of these two filaments. Black phosphorus nanosheets were added to alginate (the shell layer) in the drug-loaded filament, endowing the scaffold with a photothermal effect under near infrared (NIR) laser irradiation. Moreover, NIR could trigger the drug release from the core/shell filaments to achieve photothermal-chemotherapy of cancer. Additionally, stem cells embedded in the core parts of the other filaments could maintain high cell viability due to the protection of the shell layer (pure alginate), which promoted soft tissue regeneration in vivo. Thus, the prepared biphasic scaffold with drug- and stem cell-laden core/shell filaments may be a potential candidate to fill the tissue defects after the surgical resection of tumors to kill the residual and recurrent cancer and repair the tissue defects.

Short-peptide amyloid assembly and disassembly play crucial roles in various research fields, which range from addressing pathologies that lack therapeutic solutions to the development of innovative soft (bio)materials. Hydrogels from short peptides typically show thermo-reversible gel-to-sol transition, whereby fibrils disassemble upon heating, and re-assemble upon cooling down to room temperature (rt). Despite ongoing intense research studies in this area, the majority focus on peptide-peptide interaction and neglect the structuring role of water in peptide supramolecular behavior. This study describes an unprotected tetrapeptide gelator that forms highly stable fibrils which, upon heating, re-organize into plates that persist upon cooling to rt. All-atom molecular dynamics (MD) simulations and experimental methods reveal water as a key player in the thermodynamics that accompany this irreversible morphological transition, and advance our understanding of supramolecular structures.

Elucidating the intrinsic relationship between disease and mitochondrial viscosity is crucial for early diagnosis. However, current mitochondrial viscosity fluorescent probes are highly dependent on mitochondrial membrane potential (MMP) and are sensitive to other mitochondrial microenvironment parameters. To address these issues, a mitochondria-targeting MMP-independent and viscosity exclusive near-infrared (NIR) fluorescent probe, ACR-DMA, was developed. ACR-DMA consists of thiophene acetonitrile as the skeleton and viscosity-sensitive unit, a pyridinium cation for the mitochondria-targeting group, and a benzyl bromide subunit for mitochondrial immobilization. It is very sensitive to viscosity and shows significant "turn-on" fluorescence behavior at 710 nm with a more than 150-fold fluorescence intensity increase. Furthermore, ACR-DMA can be firmly immobilized in mitochondria and can monitor viscosity changes induced by nystain, monensin, and lipopolysaccharide. Additionally, it was successfully used to visualize mitochondrial viscosity changes resulting from tumors, inflammation, and drug-induced acute kidney injury, revealing the relationship between viscosity and disease both in vitro and in vivo. ACR-DMA is expected to be a promising candidate for diagnosing mitochondrial viscosity-related diseases.

The extracellular matrix (ECM) is a dynamic environment that is primarily built up from fibrous proteins (e.g., elastins, fibronectins, collagens, and laminins) and plays a vital role in tissue regeneration processes. Therefore, the development of supramolecular hydrogels that can mimic the ECM's dynamicity and fibrous structure is of great interest in regenerative medicine. However, such hydrogels generally have weak mechanical properties and poor structural stability, which significantly limits their potential applications. To overcome this drawback, we developed a new type of hybrid network composed of supramolecular assemblies with covalent nanoparticle-based crosslinkers. The ECM mimetic hydrogels were created through UV-initiated thiol-ene crosslinking between norbornene functionalized benzene-1,3,5-tri carboxamide (NBTA) macromonomers and thiol functionalized mesoporous silica nanoparticles (MSN). We hypothesized that the MSN would improve the mechanical properties by crosslinking the NBTA supramolecular fibrous hydrogels. Notably, the covalent incorporation of MSNs did not disrupt the fibrous morphology of the resulting NBTA-MSN nanocomposites. Furthermore, these supramolecular nanocomposites demonstrated higher structural stability and elasticity compared to pristine NBTA hydrogels. Rheology studies showed that the mechanical properties of NBTA-MSN hydrogels could be tuned by adjusting MSN wt%. Interestingly, NBTA-MSN nanocomposites exhibited self-healing and injectability despite the covalent crosslinking of MSNs. In vitro studies confirmed that NBTA-MSN nanocomposites showed good cytocompatibility and maintained the viability of encapsulated MG63 cells. As a proof of concept, we also demonstrated that MSNs could act as ion reservoirs for calcium and phosphate within the hydrogel networks in addition to being covalent crosslinkers. Taken together, our work offers a promising strategy to create hybrid, biomimetic supramolecular nanocomposite materials for various applications such as injectable materials for bone tissue engineering, and reinforced bioinks for 3D printing applications.

Free radical therapy, based on the sulfate radical derived from peroxymonosulfate, has recently been explored as a potential cancer treatment. However, while it is promising, its successful application is restricted by several limitations including the uncontrollable generation of free radicals and the instability in aqueous medium. Herein, we prepared LCP nanoparticles by using PMS as a core, the Co-coordination polymer (Co-CP) as a coating layer, and lactobionic acid as a targeting ligand for hepatoma carcinoma cells. LCP could be activated by cobalt ions released from Co-CP, and successfully induced apoptosis and ferroptosis via the inhibition of glutathione peroxidase 4 and caused the accumulation of lipid peroxidation to enhance the efficacy of free radical therapy.

Fluorescent dyes (especially photoconvertible cyanine dyes) are traditionally used as labels to study single-cell or cell-group interactions and migration. Nevertheless, their application has some disadvantages, such as cytotoxicity and dye transfer between cells during co-cultivation. The latter can lead to serious distortions in research results. At the same time, the lack of a worthy alternative explains the reasons for hushing up this serious problem. Here, we propose low-cytotoxicity encapsulated forms of cyanine 3.5 and cyanine 5.5, enabling intracellular uptake and facilitating single-cell labeling and tracking as an efficient alternative to existing staining. Only 16.9% of myoblasts (C2C12) exchanged encapsulated dyes compared with 99.7% of cells that exchanged the free form of the same dyes. Simultaneous application of several encapsulated cyanine dyes, combined with the possibility of photoconversion, provides multi-color coding of individual cells. Encapsulation of cyanine dyes allows reliable labeling and reduces the transfer of the dyes between cells.

Injectable hydrogels have been extensively studied due to their minimally invasive properties, ease of application, and void-filling properties. In this work, we tested the possibility to prepare a new type of gels, so called eutectogels, where water is replaced by a natural deep eutectic system (NADES), conferring it longer stability. Eutectogels based on betaine : glycerol 1 : 2, were prepared by enzymatic mediated crosslinking, using horseradish peroxidase (HRP) as catalyst and gelatine-phenol conjugated polymer. In comparison to hydrogels, that required higher enzyme concentration (15 U mL^-1) to have gelation time under 2 minutes, the eutectogels were obtained using 10 and 5 U mL^-1 of HRP, with gelation times of 30 and 50 seconds, respectively. Finally, ketoprofen was loaded into the polymeric matrix, and release studies were conducted. The presence of NADES was essential for the formulation of the drug loaded gel, which was able to release up to 70% of the drug within 10 days, therefore, it was possible to conclude that these eutectogels work as matrix for the controlled delivery of ketoprofen in aqueous medium. The in vitro biological evaluation of the individual components of the eutectogel support no cytotoxic effect, an early indication of potential biocompatibility.

Immuno-photodynamic therapy (IPDT) has become a promising approach for cancer treatment. Innovative photosensitizers are essential to fully realize the potential of IPDT, specifically the complete elimination of tumors without recurrence. In this context, Jong Seung Kim et al. introduce a small molecule photosensitizer conjugate, LuCXB. This IPDT agent combines a celecoxib (cyclooxygenase-2 inhibitor) moiety with a near-infrared absorbing lutetium texaphyrin photocatalytic core. In aqueous solutions, the two components of LuCXB self-associate through inferred donor-acceptor interactions. As a result of this intramolecular association, LuCXB generates superoxide radicals (O₂^-˙) via a type I photodynamic pathway upon irradiation with 730 nm light. This serves as a primary defense against the tumor and enhances the IPDT effect. For in vivo applications, they developed a CD133-targeting, aptamer-functionalized exosome-based nanophotosensitizer (Ex-apt@LuCXB) aimed at targeting cancer stem cells. Ex-apt@LuCXB demonstrated excellent photosensitivity, satisfactory biocompatibility, and strong tumor-targeting capabilities. Under photoirradiation, Ex-apt@LuCXB amplifies IPDT and produces significant antitumor effects in liver and breast cancer mouse models. The therapeutic outcomes are attributed to a synergistic mechanism that combines antiangiogenesis with photoinduced cancer immunotherapy.

Nanobiopolymers have emerged as a transformative frontier in cancer treatment, leveraging nanotechnology to transform drug delivery. This review provides a comprehensive exploration of the multifaceted landscape of nano-based biopolymers, emphasizing their diverse sources, synthesis methods, and classifications. Natural, synthetic, and microbial nanobiopolymers are scrutinized, along with elucidation of their underlying mechanisms and impact on cancer drug delivery; the latest findings on their deployment as targeted drug delivery agents for cancer treatment are discussed. A detailed analysis of nanobiopolymer sources, including polysaccharides, peptides, and nucleic acids, highlights critical attributes like biodegradability, renewability, and sustainability essential for therapeutic applications. The classification of nanobiopolymers based on their origin and differentiation among natural, synthetic, and microbial sources are thoroughly examined for inherent advantages, challenges, and suitability for cancer therapeutics. The importance of targeted drug release at tumour sites, crucial for minimizing adverse effects on normal tissues, is discussed, encompassing various mechanisms. The role of polymer membrane coatings as a pivotal barrier for facilitating controlled drug release through diffusion is elucidated, providing further insight into efficient methods for cancer treatment and thus consolidating the current knowledge base for researchers and practitioners in the field of nanobiopolymers and cancer therapeutics.

Supramolecular bioinspired self-assembling peptide hydrogel (SAPH) scaffolds represent a class of fully defined synthetic materials whose chemical and mechanical properties can be finely engineered. In this study, the relationship between SAPHs physicochemical properties and HepG2 cells viability, spheroid formation and function are discussed. We first report that negatively charged SAPHs promote hepatocyte proliferation and spheroids formation in vitro 3D culture while positively charged SAPHs lead to hepatocyte death irrespective of the hydrogel mechanical properties. More specifically HepG2 cultured in 3D in E(FKFE)₂ negatively charged SAPH maintained a differentiated phenotype and assembled into well-defined spheroids with strong cell-cell interactions. Furthermore, HepG2 spheroids responded to acetaminophen exposure with upregulation of key CYP450 enzymes expression clearly showing their potential for drug toxicity testing. These findings demonstrate how fine-tuned functional SAPH scaffolds can be used to identify key scaffolds parameters affecting cells. In this case we demonstrated the potential of negatively charged SAPHs for the 3D culture of HepG2 with potential applications in drug screening.