Transition Metal (Molybdenum)-Doped Drug-like Conformational Nanoarchitectonics with Altered Valence States (Mn2+/Mn4+ and Mo5+/Mo6+) for Augmented Cancer Theranostics.

Despite the advancements in cancer therapy, delivering active pharmaceutical ingredients (APIs) using nanoparticles remains challenging due to the failed conveyance of the required drug payload, poor targeting ability, and poor biodistribution, hampering their clinical translation. Recently, the appropriate design of materials with intrinsic therapeutic functionalities has garnered enormous interest in the development of various intelligent therapeutic nanoplatforms. In this study, we demonstrate the fabrication of transition metal (molybdenum, Mo)-doped manganese dioxide (MnO2) nanoarchitectures, exhibiting diagnostic (magnetic resonance imaging, MRI) and therapeutic (chemodynamic therapy, CDT) functionalities. The facile hydrothermal approach-assisted Mo-doped MnO2 flower-like nanostructures offered tailorable morphologies in altered dimensions, precise therapeutic effects, exceptional biocompatibility, and biodegradability in the tumor microenvironment. The resultant defects due to doped Mo species exhibited peroxidase and oxidase activities, improving glutathione (GSH) oxidation. The two sets of variable valence metal ion pairs (Mn2+/Mn4+ and Mo5+/Mo6+) and their interplay could substantially improve the Fenton-like reaction and generate toxic hydroxyl radicals (•OH), thus achieving CDT-assisted antitumor effects. As inherent T1-MRI agents, these MnO2 nanoparticles displayed excellent MRI efficacy in vitro. Together, we believe that these conformational Mo-doped MnO2 nanoarchitectures with two pairs of variable valence states could potentiate drugless therapy in pharmaceutics.

Engineered liver-derived decellularized extracellular matrix-based three-dimensional tumor constructs for enhanced drug screening efficiency.

The decellularized extracellular matrix (dECM) has emerged as an effective medium for replicating the in vivo-like conditions of the tumor microenvironment (TME), thus enhancing the screening accuracy of chemotherapeutic agents. However, recent dECM-based tumor models have exhibited challenges such as uncontrollable morphology and diminished cell viability, hindering the precise evaluation of chemotherapeutic efficacy. Herein, we utilized a tailor-made microfluidic approach to encapsulate dECM from porcine liver in highly poly(lactic-co-glycolic acid) (PLGA) porous microspheres (dECM-PLGA PMs) to engineer a three-dimensional (3D) tumor model. These dECM-PLGA PMs-based microtumors exhibited significant promotion of hepatoma carcinoma cells (HepG2) proliferation compared to PLGA PMs alone, since the infusion of extracellular matrix (ECM) microfibers and biomolecular constituents within the PMs. Proteomic analysis of the dECM further revealed the potential effects of these bioactive fragments embedded in the PMs. Notably, dECM-PLGA PMs-based microtissues effectively replicated the drug resistance traits of tumors, showing pronounced disparities in half-maximal inhibitory concentration (IC50) values, which could correspond with certain aspects of the TME. Collectively, these dECM-PLGA PMs substantially surmounted the prevalent challenges of unregulated microstructure and suboptimal cell viability in conventional 3D tumor models. They also offer a sustainable and scalable platform for drug testing, holding promise for future pharmaceutical evaluations.

Decellularised extracellular matrix-based injectable hydrogels for tissue engineering applications.

Decellularised extracellular matrix (dECM) is a biomaterial derived from natural tissues that has attracted considerable attention from tissue engineering researchers due to its exceptional biocompatibility and malleability attributes. These advantageous properties often facilitate natural cell infiltration and tissue reconstruction for regenerative medicine. Due to their excellent fluidity, the injectable hydrogels can be administered in a liquid state and subsequently formed into a gel state in vivo, stabilising the target area and serving in a variety of ways, such as support, repair, and drug release functions. Thus, dECM-based injectable hydrogels have broad prospects for application in complex organ structures and various tissue injury models. This review focuses on exploring research advances in dECM-based injectable hydrogels, primarily focusing on the applications and prospects of dECM hydrogels in tissue engineering. Initially, the recent developments of the dECM-based injectable hydrogels are explained, summarising the different preparation methods with the evaluation of injectable hydrogel properties. Furthermore, some specific examples of the applicability of dECM-based injectable hydrogels are presented. Finally, we summarise the article with interesting prospects and challenges of dECM-based injectable hydrogels, providing insights into the development of these composites in tissue engineering and regenerative medicine.

Decellularized extracellular matrix-based disease models for drug screening.

In vitro drug screening endeavors to replicate cellular states closely resembling those encountered in vivo, thereby maximizing the fidelity of drug effects and responses within the body. Decellularized extracellular matrix (dECM)-based materials offer a more authentic milieu for crafting disease models, faithfully emulating the extracellular components and structural complexities encountered by cells in vivo. This review discusses recent advancements in leveraging dECM-based materials as biomaterials for crafting cell models tailored for drug screening. Initially, we delineate the biological functionalities of diverse ECM components, shedding light on their potential influences on disease model construction. Further, we elucidate the decellularization techniques and methodologies for fabricating cell models utilizing dECM substrates. Then, the article delves into the research strides made in employing dECM-based models for drug screening across a spectrum of ailments, including tumors, as well as heart, liver, lung, and bone diseases. Finally, the review summarizes the bottlenecks, hurdles, and promising research trajectories associated with the dECM materials for drug screening, alongside their prospective applications in personalized medicine. Together, by encapsulating the contemporary research landscape surrounding dECM materials in cell model construction and drug screening, this review underscores the vast potential of dECM materials in drug assessment and personalized therapy.

ß-Cyclodextrin-based nanoassemblies for the treatment of atherosclerosis.

Atherosclerosis, a chronic and progressive condition characterized by the accumulation of inflammatory cells and lipids within artery walls, remains a leading cause of cardiovascular diseases globally. Despite considerable advancements in drug therapeutic strategies aimed at managing atherosclerosis, more effective treatment options for atherosclerosis are still warranted. In this pursuit, the emergence of ß-cyclodextrin (ß-CD) as a promising therapeutic agent offers a novel therapeutic approach to drug delivery targeting atherosclerosis. The hydrophobic cavity of ß-CD facilitates its role as a carrier, enabling the encapsulation and delivery of various therapeutic compounds to affected sites within the vasculature. Notably, ß-CD-based nanoassemblies possess the ability to reduce cholesterol levels, mitigate inflammation, solubilize hydrophobic drugs and deliver drugs to affected tissues, making these nanocomponents promising candidates for atherosclerosis management. This review focuses on three major classes of ß-CD-based nanoassemblies, including ß-CD derivatives-based, ß-CD/polymer conjugates-based and polymer ß-CD-based nanoassemblies, highlighting a variety of formulations and assembly methods to improve drug delivery and therapeutic efficacy. These ß-CD-based nanoassemblies exhibit a variety of therapeutic mechanisms for atherosclerosis and offer systematic strategies for overcoming barriers to drug delivery. Finally, we discuss the present obstacles and potential opportunities in the development and application of ß-CD-based nanoassemblies as novel therapeutics for managing atherosclerosis and addressing cardiovascular diseases.

Biosensing of Cysteine through the Induction of Oxygen Vacancies in a Cu/Zr Heterostructure Prepared by Supercritical Antisolvent Technique.

There has been a growing emphasis on facile preparation of binary heterogeneous composite materials. Leveraging the eco-friendly efficiency of supercritical CO2 technology, we achieved precise control over the influencing factors of mass transfer, enabling the accurate modulation of the resulting product morphology and properties. In the current study, CuxO/ZrOy composite materials were prepared using this technology and calcined to obtain electrode materials for the detection of cysteine (Cys). Essential comprehensive characterization techniques were employed to elucidate the heterojunction. The resulting electrode demonstrated a linear response to Cys within a concentration range of 0.5 nM to 1 µM, featuring a high sensitivity of 1035 µA·cm-2·µM-1 and a low detection limit of 97.3 nM. Thus, establishing a novel avenue for nonenzyme-based electrochemical sensors tailored for biologically active Cys detection through the implementation of a heterogeneous structure.

Recent advances in fabrication of dECM-based composite materials for skin tissue engineering.

Chronic wound management is an intractable medical and social problem, affecting the health of millions worldwide. Decellularized extracellular matrix (dECM)-based materials possess remarkable biological properties for tissue regeneration, which have been used as commercial products for skin regeneration in clinics. However, the complex external environment and the longer chronic wound-healing process hinder the application of pure dECM materials. dECM-based composite materials are constructed to promote the healing process of different wounds, showing noteworthy functions, such as anti-microbial activity and suitable degradability. Moreover, fabrication technologies for designing wound dressings with various forms have expanded the application of dECM-based composite materials. This review provides a summary of the recent fabrication technologies for building dECM-based composite materials, highlighting advances in dECM-based molded hydrogels, electrospun fibers, and bio-printed scaffolds in managing wounds. The associated challenges and prospects in the clinical application of dECM-based composite materials for wound healing are finally discussed.

NIR-switchable local hydrogen generation by tandem bimetallic MOFs nanocomposites for enhanced chemodynamic therapy.

The inadequate quantity of hydrogen peroxide (H2O2) in cancer cells promptly results in the constrained success of chemodynamic therapy (CDT). Significant efforts made throughout the years; nevertheless, researchers are still facing the great challenge of designing a CDT agent and securing H2O2 supply within the tumor cell. In this study, taking advantage of H2O2 level maintenance mechanism in cancer cells, a nanozyme-based bimetallic metal-organic frameworks (MOFs) tandem reactor is fabricated to elevate intracellular H2O2 levels, thereby enhancing CDT. In addition, under near-infrared excitation, the upconversion nanoparticles (UCNPs) loaded into the MOFs can perform photocatalysis and generate hydrogen, which increases cellular susceptibility to radicals induced from H2O2, inhibits cancer cell energy, causes DNA damages and induces tumor cell apoptosis, thus improving CDT therapeutic efficacy synergistically. The proposed nanozyme-based bimetallic MOFs-mediated CDT and UCNPs-mediated hydrogen therapy act as combined therapy with high efficacy and low toxicity.

Decellularized extracellular matrix-based composite scaffolds for tissue engineering and regenerative medicine.

Despite the considerable advancements in fabricating polymeric-based scaffolds for tissue engineering, the clinical transformation of these scaffolds remained a big challenge because of the difficulty of simulating native organs/tissues' microenvironment. As a kind of natural tissue-derived biomaterials, decellularized extracellular matrix (dECM)-based scaffolds have gained attention due to their unique biomimetic properties, providing a specific microenvironment suitable for promoting cell proliferation, migration, attachment and regulating differentiation. The medical applications of dECM-based scaffolds have addressed critical challenges, including poor mechanical strength and insufficient stability. For promoting the reconstruction of damaged tissues or organs, different types of dECM-based composite platforms have been designed to mimic tissue microenvironment, including by integrating with natural polymer or/and syntenic polymer or adding bioactive factors. In this review, we summarized the research progress of dECM-based composite scaffolds in regenerative medicine, highlighting the critical challenges and future perspectives related to the medical application of these composite materials.

Protein-guided biomimetic nanomaterials: a versatile theranostic nanoplatform for biomedical applications.

Over the years, bioinspired mineralization-based approaches have been applied to synthesize multifunctional organic-inorganic nanocomposites. These nanocomposites can address the growing demands of modern biomedical applications. Proteins, serving as vital biological templates, play a pivotal role in the nucleation and growth processes of various organic-inorganic nanocomposites. Protein-mineralized nanomaterials (PMNMs) have attracted significant interest from researchers due to their facile and convenient preparation, strong physiological activity, stability, impressive biocompatibility, and biodegradability. Nevertheless, few comprehensive reviews have expounded on the progress of these nanomaterials in biomedicine. This article systematically reviews the principles and strategies for constructing nanomaterials using protein-directed biomineralization and biomimetic mineralization techniques. Subsequently, we focus on their recent applications in the biomedical field, encompassing areas such as bioimaging, as well as anti-tumor, anti-bacterial, and anti-inflammatory therapies. Furthermore, we discuss the challenges encountered in practical applications of these materials and explore their potential in future applications. This review aspired to catalyze the continued development of these bioinspired nanomaterials in drug development and clinical diagnosis, ultimately contributing to the fields of precision medicine and translational medicine.

Surface-modified titanium and titanium-based alloys for improved osteogenesis: A critical review.

As implantable materials, titanium, and its alloys have garnered enormous interest from researchers for dental and orthopedic procedures. Despite their success in wide clinical applications, titanium, and its alloys fail to stimulate osteogenesis, resulting in poor bonding strength with surrounding bone tissue. Optimizing the surface topology and altered compositions of titanium and titanium-based alloys substantially promotes peri-implant bone regeneration. This review summarizes the utilization and importance of various osteogenesis components loaded onto titanium and its alloys. Further, different surface-modification methods and the release efficacy of loaded substances are emphasized. Finally, we summarize the article with prospects. We believe that further investigation studies must focus on identifying novel loading components, exploring various innovative, optimized surface-modification methods, and developing a sustained-release system on implant surfaces to improve peri-implant bone formation.

Fluoride-Free Synthesis of 2D Titanium Carbide (MXenes) Assisted by scCO2 -Based Ternary Solution.

2D MXene-Ti3 C2 Tx holds great promise in various electronic applications, especially for electromagnetic interference (EMI) shielding devices and supercapacitors. Ti3 C2 Tx synthesis typically involves the use of hazardous fluorine-containing chemicals that can result in the formation of inert fluoride functional groups on the surface of Ti3 C2 Tx , severely degrading its properties and posing a threat to the performance of electron transfer among electrical devices. Herein, a supercritical carbon dioxide-based ternary solution (scCO2 /DMSO/HCl) to produce fluoride-free Ti3 C2 Tx in mild conditions (via 0.5 m HCl, 20 MPa, 32 °C) is reported. The fluorine-free Ti3 C2 Tx films electrode presents an excellent gravimetric capacitance of 320 F g-1 at 2 mV s-1 in 1 m H2 SO4 . Besides, it is demonstrated that fluorine-free Ti3 C2 Tx films exhibit outstanding EMI shielding efficiency of 53.12 dB at 2.5 µm thickness. The findings offer a mild and practical approach to producing fluoride-free Ti3 C2 Tx and open opportunities for exploring MXenes' potential applications in various fields.

Transition Metal Oxide-Decorated MXenes as Drugless Nanoarchitectonics for Enriched Nanocatalytic Chemodynamic Treatment.

Despite their unique characteristics, 2D MXenes with sole photothermal conversion ability are required to explore their superfluous abilities in biomedicine. The small-molecule-based chemotherapeutics suffer from various shortcomings of time-consuming and expensiveness concerning theoretical and performance (preclinical/clinical) checks. This study demonstrates the fabrication of Ti3C2 MXene nanosheets (TC-MX NSs) and subsequent decoration with transition metal oxides, that is, copper oxide (Cu2O/MX, CO-MX NCs) as drugless nanoarchitectonics for synergistic photothermal (PTT)-chemodynamic therapeutic (CDT) efficacies. Initially, the monolayer/few-layered TC-MX NSs are prepared using the chemical etching-assisted ultrasonic exfoliation method and then deposited with Cu2O nanoconstructs using the in situ reduction method. Further, the photothermal ablation under near-infrared (NIR)-II laser irradiation shows PTT effects of CO-MX NCs. The deposited Cu2O on TC-MX NSs facilitates the release of copper (Cu+) ions in the acidic microenvironment intracellularly for Fenton-like reaction-assisted CDT effects and enriched PTT effects synergistically. Mechanistically, these deadly free radicals intracellularly imbalance the glutathione (GSH) levels and result in mitochondrial dysfunction, inducing apoptosis of 4T1 cells. Finally, the in vivo investigations in BALB/c mice confirm the substantial ablation of breast carcinoma. Together, these findings demonstrate the potential synergistic PTT-CDT effects of the designed CO-MX NCs as drugless nanoarchitectonics against breast carcinoma.

NIR-II light triggered burst-release cascade nanoreactor for precise cancer chemotherapy.

The current strategy of co-delivering copper ions and disulfiram (DSF) to generate cytotoxic CuET faces limitations in achieving rapid and substantial CuET production, specifically in tumor lesions. To overcome this challenge, we introduce a novel burst-release cascade reactor composed of phase change materials (PCMs) encapsulating ultrasmall Cu2-xSe nanoparticles (NPs) and DSF (DSF/Cu2-xSe@PCM). Once triggered by second near-infrared (NIR-II) light irradiation, the reactor swiftly releases Cu2-xSe NPs and DSF, enabling catalytic reactions that lead to the rapid and massive production of Cu2-xSe-ET complexes, thereby achieving in situ chemotherapy. The mechanism of the burst reaction is due to the unique properties of ultrasmall Cu2-xSe NPs, including their small size, multiple defects, and high surface activity. These characteristics allow DSF to be directly reduced and chelated on the surface defect sites of Cu2-xSe, forming Cu2-xSe-ET complexes without the need for copper ion release. Additionally, Cu2-xSe-ET has demonstrated a similar (to CuET) anti-tumor activity through increased autophagy, but with even greater potency due to its unique two-dimensional-like structure. The light-triggered cascade of interlocking reactions, coupled with in situ explosive generation of tumor-suppressive substances mediated by the size and valence of Cu2-xSe, presents a promising approach for the development of innovative nanoplatforms in the field of precise tumor chemotherapy.

NIR-responsive carrier-free nanoparticles based on berberine hydrochloride and indocyanine green for synergistic antibacterial therapy and promoting infected wound healing.

Bacterial infections cause severe health conditions, resulting in a significant economic burden for the public health system. Although natural phytochemicals are considered promising anti-bacterial agents, they suffer from several limitations, such as poor water solubility and low bioavailability in vivo, severely restricting their wide application. Herein, we constructed a near-infrared (NIR)-responsive carrier-free berberine hydrochloride (BH, phytochemicals)/indocyanine green (ICG, photosensitizer) nanoparticles (BI NPs) for synergistic antibacterial of an infected wound. Through electrostatic interaction and π-π stacking, the hydrophobic BH and amphiphilic ICG are initially self-assembled to generate carrier-free nanoparticles. The obtained BI NPs demonstrated NIR-responsive drug release behavior and better photothermal conversion efficiency of up to 36%. In addition, BI NPs stimulated by NIR laser exhibited remarkable antibacterial activity, which realized the synergistic antibacterial treatment and promoted infected wound healing. In summary, the current research results provided a candidate strategy for self-assembling new BI NPs to treat bacterial infections synergistically.

Sonodynamic therapy-based nanoplatforms for combating bacterial infections.

The rapid spread and uncontrollable evolution of antibiotic-resistant bacteria have already become urgent global to treat bacterial infections. Sonodynamic therapy (SDT), a noninvasive and effective therapeutic strategy, has broadened the way toward dealing with antibiotic-resistant bacteria and biofilms, which base on ultrasound (US) with sonosensitizer. Sonosensitizer, based on small organic molecules or inorganic nanoparticles, is essential to the SDT process. Thus, it is meaningful to design a sonosensitizer-loaded nanoplatform and synthesize the nanoplatform with an efficient SDT effect. In this review, we initially summarize the probable SDT-based antibacterial mechanisms and systematically discuss the current advancement in different SDT-based nanoplatform (including nanoplatform for organic small-molecule sonosensitizer delivery and nanoplatform as sonosensitizer) for bacterial infection therapy. In addition, the biomedical applications of SDT-involved multifunctional nanoplatforms are also discussed. We believe the innovative SDT-based nanoplatforms would become a highly efficient next-generation noninvasive therapeutic tool for combating bacterial infection.

Observing the Evolution of Metal Oxides in Liquids.

Metal oxides with diverse compositions and structures have garnered considerable interest from researchers in various reactions, which benefits from transmission electron microscopy (TEM) in determining their morphologies, phase, structural and chemical information. Recent breakthroughs have made liquid-phase TEM a promising imaging platform for tracking the dynamic structure, morphology, and composition evolution of metal oxides in solution under work conditions. Herein, this review introduces the recent advances in liquid cells, especially closed liquid cell chips. Subsequently, the recent progress including particle growth, phase transformation, self-assembly, core-shell nanostructure growth, and chemical etching are introduced. With the late technical advances in TEM and liquid cells, liquid-phase TEM is used to characterize many fundamental processes of metal oxides for CO2 reduction and water-splitting reactions. Finally, the outlook and challenges in this research field are discussed. It is believed this compilation inspires and stimulates more efforts in developing and utilizing in situ liquid-phase TEM for metal oxides at the atomic scale for different applications.

Nature-inspired nanocarriers for improving drug therapy of atherosclerosis.

Atherosclerosis (AS) has emerged as one of the prevalent arterial vascular diseases characterized by plaque and inflammation, primarily causing disability and mortality globally. Drug therapy remains the main treatment for AS. However, a series of obstacles hinder effective drug delivery. Nature, from natural micro-/nano-structural biological particles like natural cells and extracellular vesicles to the distinctions between the normal and pathological microenvironment, offers compelling solutions for efficient drug delivery. Nature-inspired nanocarriers of synthetic stimulus-responsive materials and natural components, such as lipids, proteins and membrane structures, have emerged as promising candidates for fulfilling drug delivery needs. These nanocarriers offer several advantages, including prolonged blood circulation, targeted plaque delivery, targeted specific cells delivery and controlled drug release at the action site. In this review, we discuss the nature-inspired nanocarriers which leverage the natural properties of cells or the microenvironment to improve atherosclerotic drug therapy. Finally, we provide an overview of the challenges and opportunities of applying these innovative nature-inspired nanocarriers.

Hybrid nanoarchitectonics of molybdenum dioxide (MoO2) and doxorubicin (DOX) for synergistic chemo-photothermal-based breast carcinoma therapy.

Cancer has emerged as one of the severe ailments due to the uncontrolled proliferation rate of cells, accounting for millions of deaths annually. Despite the availability of various treatment strategies, including surgical interventions, radiation, and chemotherapy, tremendous advancements in the past two decades of research have evidenced the generation of different nanotherapeutic designs toward providing synergistic therapy. In this study, we demonstrate the assembly of a versatile nanoplatform based on the hyaluronic acid (HA)-coated molybdenum dioxide (MoO2) assemblies to act against breast carcinoma. The hydrothermal approach-assisted MoO2 constructs are immobilized with doxorubicin (DOX) molecules on the surface. Further, these MoO2-DOX hybrids are encapsulated with the HA polymeric framework. Furthermore, the versatile nanocomposites of HA-coated MoO2-DOX hybrids are systematically characterized using various characterization techniques, and explored biocompatibility in the mouse fibroblasts (L929 cell line), as well as synergistic photothermal (808-nm laser irradiation for 10 min, 1 W/cm2) and chemotherapeutic properties against breast carcinoma (4T1 cells). Finally, the mechanistic views concerning the apoptosis rate are explored using the JC-1 assay to measure the intracellular mitochondrial membrane potential (MMP) levels. In conclusion, these findings indicated excellent photothermal and chemotherapeutic efficacies, exploring the enormous potential of MoO2 composites against breast cancer.

Study on galactosylated sodium alginate for enhancing HepG2 Cells adhesion and 3D printability.

Sodium alginate is a polyanionic natural polysaccharide polymer widely used in tissue engineering. However, the lack of binding domains for interaction with cells limits its application in regenerative medicine. This study designed a kind of galactosylated sodium alginate (G-SA) material with improved galactose grafting rate by EDC/NHS activation of carboxyl groups in MES buffer and subsequently cross-linking by Ca2+ aims to enhance the adherence behavior of HepG2 cells on alginate substrate. The synthesized G-SA was characterized by Fourier transform infrared spectra and nuclear magnetic resonance spectroscopy. G-SA exhibited good biocompatibility and significantly enhanced the adhesion behavior of HepG2 cells on its surface. Furthermore, we demonstrated that the effect of G-SA concentration in enhancing cell adhesion was diminished at higher than 2% w/v. Finally, the suitability of G-SA material is investigated for 3D printing, demonstrating that HepG2 cells could maintain high viability and excellent printability in the interior of the gel. In addition, cells could multiply and grow into cell spheroids with an average size of 200 µm in G-SA scaffolds. These results indicated that galactosylated sodium alginate material could be used as a 3D culture system that could be effective for engineering liver cancer models.