Synthesis of cyclodextrin-based polyrotaxanes and polycatenanes for supramolecular pharmaceutical sciences.

Cyclodextrins (CDs) are essential in the pharmaceutical industry and have long been used as food and pharmaceutical additives. CD-based interlocked molecules, such as rotaxanes, polyrotaxanes, catenanes, and polycatenanes, have been synthesized and have attracted considerable attention in supramolecular chemistry. Among them, CD polyrotaxanes have been employed as slide-ring materials and biomaterials. CD polycatenanes are new materials; therefore, to date, no examples of applied research on CD polycatenanes have been reported. Consequently, we expect that applied research on CD polycatenanes will accelerate in the future. This review article summarizes the syntheses and structural analyses of CD polyrotaxanes and polycatenanes to facilitate their applications in the pharmaceutical industry. We believe that this review will promote further research on CD-based interlocked molecules.

Recent Progress on Second Near-Infrared Emitting Carbon Dots in Biomedicine.

Second near-infrared (NIR-II) carbon dots, with absorption or emission between 1000 and 1700 nm, are gaining increasing attention in the biomaterial field due to their distinctive properties, which include straightforward preparation processes, stable photophysical characteristics, excellent biocompatibility, and low cost. As a result, there is a growing focus on the controlled synthesis and modulation of the photochemical and photophysical properties of NIR-II carbon dots, with the aim to further expand their biomedical applications, a current research hotspot. This account aims to provide a comprehensive overview of the recent advancements in NIR-II carbon dots within the biomedical field. The review will cover the following topics: (i) the design, synthesis, and purification of NIR-II carbon dots, (ii) the surface modification strategies, and (iii) the biomedical applications, particularly in the domain of cancer theranostics. Additionally, this account addresses the challenges encountered by NIR-II carbon dots and will outline future directions in the realm of cancer theranostics. By exploring carbon-based NIR-II biomaterials, we can anticipate that this contribution will garner increased attention and contribute to the development of next-generation advanced functional carbon dots, thereby offering enhanced tools and strategies in the biomedical field.

Self-assembly of peptides in living cells for disease theranostics.

The past few decades have witnessed substantial progress in biomedical materials for addressing health concerns and improving disease therapeutic and diagnostic efficacy. Conventional biomedical materials are typically created through an ex vivo approach and are usually utilized under physiological environments via transfer from preparative media. This transfer potentially gives rise to challenges for the efficient preservation of the bioactivity and implementation of theranostic goals on site. To overcome these issues, the in situ synthesis of biomedical materials on site has attracted great attention in the past few years. Peptides, which exhibit remarkable biocompability and reliable noncovalent interactions, can be tailored via tunable assembly to precisely create biomedical materials. In this review, we summarize the progress in the self-assembly of peptides in living cells for disease diagnosis and therapy. After a brief introduction to the basic design principles of peptide assembly systems in living cells, the applications of peptide assemblies for bioimaging and disease treatment are highlighted. The challenges in the field of peptide self-assembly in living cells and the prospects for novel peptide assembly systems towards next-generation biomaterials are also discussed, which will hopefully help elucidate the great potential of peptide assembly in living cells for future healthcare applications.

Biocompatible Gold Nanoparticles-Modified Fluorine Doped Tin Oxide Electrode for the Fabrication of Enzyme-Free Glucose Sensor.

This work demonstrates the use of jute stick extract as a reducing and stabilizing agent for the synthesis of spherical gold nanoparticles (AuNPs). In UV-Vis spectroscopy, peak at 550 nm was used to confirm the formation of AuNPs. The spherical surface morphology of AuNPs was determined through SEM and TEM analysis. While XRD investigation revealed the crystallinity of the prepared AuNPs. To ensure the biocompatibility of synthesized AuNPs, a bacterial investigation was conducted with negative results towards bacterial strain. The, modified FTO with AuNPs were able to detect glucose in CV analysis and the constructed sensor displayed a wide linear range of 50 µM to 40 mM with a detection limit of 20 µM. Scan rate analysis was performed to determine the charge transfer coefficient (0.42) and Tafel slope (102 mV/decade). Furthermore, the interfacial surface mechanism is illustrated to understand the interaction of glucose with the electrode surface in an alkaline medium and the product formation through the dehydrogenation and hydrolysis process. The prepared sensor also showed good stability, reproducibility, and anti-interference capabilities. In the case of real sample analysis, we used a blood serum sample. A low RSD value (<10 %) suggests the practical use of AuNPs/FTO in real-life applications.

Estudio de biocompatibilidad de matrices poliméricas combinadas, responsivas al pH, con aplicación en Ingeniería de Tejido Óseo / Biocompatibility study of combined pH-responsive polymeric matrices with application in Bone Tissue Engineering

El presente trabajo muestra la obtención de un material a partir de un polímero sintético (TerP) y otro natural, mediante entrecruzamiento físico y su caracterización fisicoquímica y biológica, con el fin de emplearlos para regeneración de tejido óseo. Las membranas fueron obtenidas por la técnica de evaporación del solvente y caracterizadas por espectroscopia FTIR, ensayos de hinchamiento, medidas de ángulo de contacto y microscopia electrónica de barrido (SEM). Se encontró que la compatibilidad entre los polímeros que la constituyen es estable a pH fisiológico y que, al incorporar mayor cantidad del TerP a la matriz, esta se vuelve más hidrofóbica y porosa. Además, teniendo en cuenta la aplicación prevista para dichos materiales, se realizaron estudios de biocompatibilidad y citotoxicidad con células progenitoras de médula ósea (CPMO) y células RAW264.7, respectivamente. Se evaluó la proliferación celular, la producción y liberación de óxido nítrico (NO) al medio de cultivo durante 24 y 48 horas y la expresión de citoquinas proinflamatorias IL-1ß y TNF-α de las células crecidas sobre los biomateriales variando la cantidad del polímero sintético. Se encontró mayor proliferación celular y menor producción de NO sobre las matrices que contienen menos proporción del TerP, además de poseer una mejor biocompatibilidad. Los resultados de este estudio muestran que el terpolímero obtenido y su combinación con un polímero natural es una estrategia muy interesante para obtener un biomaterial con posibles aplicaciones en medicina regenerativa y que podría extenderse a otros sistemas estructuralmente relacionados. (AU)

In the present work, the preparation of a biomaterial from a synthetic terpolymer (TerP) and a natural polymer, physically crosslinked, is shown. In order to evaluate the new material for bone tissue regeneration, physicochemical and biological characterizations were performed. The membranes were obtained by solvent casting and characterized using FTIR spectroscopy, swelling tests, contact angle measurements, and scanning electron microscopy (SEM). It was found that the compatibility between the polymers is stable at physiological pH and the incorporation of a higher amount of TerP into the matrix increases hydrophobicity and porosity.Furthermore, considering the intended application of these materials, studies of biocompatibility and cytotoxicity were conducted with Bone Marrow Progenitor Cells (BMPCs) and RAW264.7 cells, respectively. Cell proliferation, NO production and release into the culture medium for 24 and 48 hours, and proinflammatory cytokine expression of IL-1ß and TNF-α from cells grown on the biomaterials while varying the amount of the synthetic polymer were evaluated. Greater cell proliferation and lower NO production were found on matrices containing a lower proportion of TerP, in addition to better biocompatibility. The results of this study demonstrate that the obtained terpolymer and its combination with a natural polymer is a highly interesting strategy for biomaterial preparation with potential applications in regenerative medicine. This approach could be extended to other structurally related systems. (AU)

Cartilage-like protein hydrogels engineered via entanglement.

Load-bearing tissues, such as muscle and cartilage, exhibit high elasticity, high toughness and fast recovery, but have different stiffness (with cartilage being significantly stiffer than muscle)1-8. Muscle achieves its toughness through finely controlled forced domain unfolding-refolding in the muscle protein titin, whereas articular cartilage achieves its high stiffness and toughness through an entangled network comprising collagen and proteoglycans. Advancements in protein mechanics and engineering have made it possible to engineer titin-mimetic elastomeric proteins and soft protein biomaterials thereof to mimic the passive elasticity of muscle9-11. However, it is more challenging to engineer highly stiff and tough protein biomaterials to mimic stiff tissues such as cartilage, or develop stiff synthetic matrices for cartilage stem and progenitor cell differentiation12. Here we report the use of chain entanglements to significantly stiffen protein-based hydrogels without compromising their toughness. By introducing chain entanglements13 into the hydrogel network made of folded elastomeric proteins, we are able to engineer highly stiff and tough protein hydrogels, which seamlessly combine mutually incompatible mechanical properties, including high stiffness, high toughness, fast recovery and ultrahigh compressive strength, effectively converting soft protein biomaterials into stiff and tough materials exhibiting mechanical properties close to those of cartilage. Our study provides a general route towards engineering protein-based, stiff and tough biomaterials, which will find applications in biomedical engineering, such as osteochondral defect repair, and material sciences and engineering.

The development of carbohydrate polymer- and protein-based biomaterials and their role in environmental health and hygiene: A review.

Biological macromolecules have been significantly used in the medicine due to their certain therapeutic values. Macromolecules have been employed in medical filed in order to enhance, support, and substitute damaged tissues or any other biological function. In the past decade, the biomaterial field has developed considerably because of vast innovations in regenerative medicine, tissue engineering, etc. Different types of biological macromolecules such as natural protein and polysaccharide etc. and synthetic molecules such as metal based, polymer based, and ceramic based etc. have been discussed. These materials can be modified by coatings, fibres, machine parts, films, foams, and fabrics for utilization in biomedical products and other environmental applications. At present, the biological macromolecules can used in different areas like medicine, biology, physics, chemistry, tissue engineering, and materials science. These materials have been used to promote the healing of human tissues, medical implants, bio-sensors and drug delivery, etc. These materials also considered as environmentally sustainable as they are prepared in association with renewable natural resources and living organisms in contrast to non-renewable resources (petrochemicals). In addition, enhanced compatibility, durability and circular economy of biological materials make them highly attractive and innovative for current research.The present review paper summarizes a brief about biological macromolecules, their classification, methods of synthesis, and their role in biomedicine, dyes and herbal products.

Simple synthesis of soft, tough, and cytocompatible biohybrid composites.

Collagen is the most abundant component of mammalian extracellular matrices. As such, the development of materials that mimic the biological and mechanical properties of collagenous tissues is an enduring goal of the biomaterials community. Despite the development of molded and 3D printed collagen hydrogel platforms, their use as biomaterials and tissue engineering scaffolds is hindered by either low stiffness and toughness or processing complexity. Here, we demonstrate the development of stiff and tough biohybrid composites by combining collagen with a zwitterionic hydrogel through simple mixing. This combination led to the self-assembly of a nanostructured fibrillar network of collagen that was ionically linked to the surrounding zwitterionic hydrogel matrix, leading to a composite microstructure reminiscent of soft biological tissues. The addition of 5-15 mg mL-1 collagen and the formation of nanostructured fibrils increased the elastic modulus of the composite system by 40% compared to the base zwitterionic matrix. Most notably, the addition of collagen increased the fracture energy nearly 11-fold ([Formula: see text] 180 J m-2) and clearly delayed crack initiation and propagation. These composites exhibit elastic modulus ([Formula: see text] 0.180 MJ) and toughness ([Formula: see text]0.617 MJ m-3) approaching that of biological tissues such as articular cartilage. Maintenance of the fibrillar structure of collagen also greatly enhanced cytocompatibility, improving cell adhesion more than 100-fold with >90% cell viability.

Fabrication of silk fibroin film enhanced by acid hydrolyzed silk fibroin nanowhiskers to improve bacterial inhibition and biocompatibility efficacy.

In this study, silk fibroin nanowhiskers (SNWs) were extracted from natural silk fiber by sulfuric acid hydrolysis with the assistance of ultrasonic wave treatment. The obtained SNWs were mixed with regenerated silk fibroin (RSF) solution to fabricate the SNWs/RSF films. The fabricating SNWs were systematically characterized by using SEM, FTIR, and the SNWs/RSF films were observed by digital camera, PM, etc. The results show that the monodisperse SNWs are evenly distributed in the RSF film. The presence of SNWs in RSF film significantly improves the performances of the film, including the swelling ability, mechanical properties, hydrophilicity, antibacterial efficacy, cytocompatibility. Meanwhile, the SNWs/RSF film can endorse the wound healing efficiency in vivo mice wound site. The proposed techniques for extracting SNWs and fabricating silk fibroin composite film may provide a valuable method for creating an ideal silk-based material for biomedical applications.

NIR-Responsive Lysosomotropic Phototrigger: An "AIE + ESIPT" Active Naphthalene-Based Single-Component Photoresponsive Nanocarrier with Two-Photon Uncaging and Real-Time Monitoring Ability.

In recent times, organelle-targeted drug delivery systems have gained tremendous attention due to the site-specific delivery of active drug molecules, resulting in enhanced bioefficacy. In this context, a phototriggered drug delivery system (DDS) for releasing an active molecule is superior, as it provides spatial and temporal control over the release. So far, a near-infrared (NIR) light-responsive organelle-targeted DDS has not yet been developed. Hence, we introduced a two-photon NIR light-responsive lysosome-targeted "AIE + ESIPT" active single-component DDS based on the naphthalene chromophore. The two-photon absorption cross section of our DDS is 142 GM at 850 nm. The DDS was converted into pure organic nanoparticles for biological applications. Our nano-DDS is capable of selective targeting, AIE luminogenic imaging, and drug release within the lysosome. In vitro studies using cancerous cell lines showed that our single-component photoresponsive nanocarrier exhibited enhanced cytotoxicity and real-time monitoring ability of drug release.

Polyoxometalate Modified by Zeolite Imidazole Framework for the pH-Responsive Electrodynamic/Chemodynamic Therapy.

Electrodynamic therapy (EDT) and chemodynamic therapy (CDT) have the potential for future tumor treatment; however, their underlying applications are greatly hindered owing to their inherent drawbacks. The combination of EDT and CDT has been considered to be an effective way to maximize the superiorities of these two ROS-based methodologies. However, the development of novel nanomaterials with "one-for-all" functions still remains a big challenge. In this work, the polyoxometalate nanoparticles (NPs) were decorated using the zeolite imidazole framework (POM@ZIF-8) in order to integrate the EDT with CDT. The resulting POM@ZIF-8 NPs can effectively induce the generation of reactive oxygen species (ROS) via a catalytic reaction on the surface of POM NPs induced by an electric field (E). At the same time, POM@ZIF-8 NPs can catalyze the intracellular H2O2 into ROS via a Fenton-like reaction, thereby achieving the combination of EDT and CDT. Besides, since ZIF-8 is acid-responsive, it can protect normal tissues and avoid side effects. Of great note is that the cytotoxicity and the apoptosis rate of the POM@ZIF-8+E group (80%) were found to be significantly higher than that of the E group (55%). As a result, a high tumor inhibition phenomenon can be observed both in vitro and in vivo. The present study thus provides an alternative concept for combinational therapeutic modality with exceptional efficacy.

Natural Small Molecules Enabled Efficient Immunotherapy through Supramolecular Self-Assembly in P53-Mutated Colorectal Cancer.

Nanomedicine, constructed from therapeutics, presents an advantage in drug delivery for cancer therapies. However, nanocarrier-based treatment systems have problems such as interbatch variability, multicomponent complexity, poor drug delivery, and carrier-related toxicity. To solve these issues, the natural molecule honokiol (HK), an anticancer agent in a phase I clinical trial (CTR20170822), was used to form a self-assembly nanoparticle (SA) through hydrogen bonding and hydrophobicity. The preparation of SA needs no molecular precursors or excipients in aqueous solution, and 100% drug-loaded SA exhibited superior tumor-targeting ability due to the enhanced permeability and retention (EPR) effect. Moreover, SA significantly enhanced the antitumor immunity relative to free HK, and the mechanism has notable selectivity to the p53 pathway. Furthermore, SA exhibited excellent physiological stability and inappreciable toxicity. Taken together, this supramolecular self-assembly strategy provides a safe and "molecular economy" model for rational design of clinical therapies and is expected to promote targeted therapy of HK, especially in colorectal cancer patients with obvious p53 status.

Glycopolymer Engineering of the Cell Surface Changes the Single Cell Migratory Direction and Inhibits the Collective Migration of Cancer Cells.

Cancer cell migration is one of the most important processes in cancer metastasis. Metastasis is the major cause of death from most solid tumors; therefore, suppressing cancer cell migration is an important means of reducing cancer mortality. Cell surface engineering can alter the interactions between cells and their microenvironment, thereby offering an effective method of controlling the migration of the cells. This paper reports that modification of the mouse melanoma (B16) cancer cell surface with glycopolymers affects the migration of the cells. Changes in cell morphology, migratory trajectories, and velocity were investigated by time-lapse cell tracking. The data showed that the migration direction is altered and diffusion slows down for modified B16 cells compared to unmodified B16 cells. When modified and unmodified B16 cells were mixed, wound-healing experiments and particle image velocimetry (PIV) analysis showed that the collective migration of unmodified B16 cells was suppressed because of vortexlike motions induced by the modified cells. The work demonstrates the important role of surface properties/modification in cancer cell migration, thereby providing new insights relative to the treatment of cancer metastasis.

Fabrication of Host-Guest Complexes between Adamantane-Functionalized 1,3,4-Oxadiazoles and ß-Cyclodextrin with Improved Control Efficiency against Intractable Plant Bacterial Diseases.

Supramolecular chemistry provides huge potentials and opportunities in agricultural pest management. In an attempt to develop highly bioactive, eco-friendly, and biocompatible supramolecular complexes for managing intractable plant bacterial diseases, herein, a type of interesting adamantane-functionalized 1,3,4-oxadiazole was rationally prepared to facilitate the formation of supramolecular complexes via ß-cyclodextrin-adamantane host-guest interactions. Initial antibacterial screening revealed that most of these adamantane-decorated 1,3,4-oxadiazoles were obviously bioactive against three typically destructive phytopathogens. The lowest EC50 values could reach 0.936 (III18), 0.889 (III18), and 2.10 (III19) µg/mL against the corresponding Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa). Next, the representative supramolecular binary complex III18@ß-CD (binding mode 1:1) was successfully fabricated and characterized by 1H nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), high-resolution mass spectrometry (HRMS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Eventually, correlative water solubility and foliar surface wettability were significantly improved after the formation of host-guest assemblies. In vivo antibacterial evaluation found that the achieved supramolecular complex could distinctly alleviate the disease symptoms and promote the control efficiencies against rice bacterial blight (from 34.6-35.7% (III18) to 40.3-43.6% (III18@ß-CD)) and kiwi canker diseases (from 41.0-42.3% (III18) to 53.9-68.0% (III18@ß-CD)) at 200 µg/mL (active ingredient). The current study can provide a feasible platform and insight for constructing biocompatible supramolecular assemblies for managing destructive bacterial infections in agriculture.

ß-Cyclodextrin-Derivative-Functionalized Graphene Oxide/Graphitic Carbon Nitride Composites with a Synergistic Effect for Rapid and Efficient Sterilization.

The nonselectivity of phototherapy and the hydrophobicity of phototherapy agents limit their application in the treatment of antibiotic-resistant bacteria. In this work, ß-cyclodextrin-derivative-functionalized graphene oxide (GO)/graphitic carbon nitride (g-C3N4) antibacterial materials (CDM/GO/CN) were designed and synthesized. CN is used as a photosensitizer for photodynamic therapy (PDT) and GO as a photothermal agent for photothermal therapy (PTT). In addition, the supramolecular host-guest complex on the substrate can not only increase the inherent water solubility of the substrate and reduce the aggregation of the photosensitizer/photothermal agent but also manipulate the interaction between the photosensitizer/photothermal agent and bacteria to capture specific bacteria. The hyperthermia caused by PTT denatures proteins on the cell membrane, allowing reactive oxygen species (ROS) to enter the cell better and kill bacteria. The specific capture of Escherichia coli CICC 20091 by mannose significantly improves the sterilization efficiency and reduces side effects. The synergistic antibacterial agent shows excellent antibacterial efficacy of over 99.25% against E. coli CICC 20091 after 10 min of 635 + 808 nm dual-light irradiation. Moreover, cell proliferation experiments show that the composite material has good biocompatibility, expected to have applications in bacterial infections.

Near-Infrared Light-Controllable Multifunction Mesoporous Polydopamine Nanocomposites for Promoting Infected Wound Healing.

The successful treatment of infected wounds requires strategies with effective antimicrobial, anti-inflammatory, and healing-promoting properties. Accordingly, the use of Cu2+ and tetracycline (TC), which can promote angiogenesis, re-epithelialization, and collagen deposition, also antibacterial activity, at the wound site, has shown application prospects in promoting infected wound repair. However, realizing controllable release to prolong action time and avoid potential toxicities is critical. Moreover, near-infrared light (NIR)-activated mesoporous polydopamine nanoparticles (MPDA NPs) reportedly exert anti-inflammatory effects by eliminating the reactive oxygen species generated during inflammatory responses. In this study, we assess whether Cu2+ and TC loaded in MPDA NPs can accelerate infected wound healing in mice. In particular, Cu2+ is chelated and immobilized on the surface of MPDA NPs, while a thermosensitive phase-change material (PCM; melting point: 39-40 °C), combined with antibiotics, was loaded into the MPDA NPs as a gatekeeper (PPMD@Cu/TC). Results show that PPMD@Cu/TC exhibits significant great photothermal properties with NIR irradiation, which induces the release of Cu2+, while inducing PCM melting and, subsequent, TC release. In combination with anti-inflammatory therapy, NIR-triggered Cu2+ and TC release enables the nanocomposite to eradicate bacterial wound infections and accelerate healing. Importantly, negligible damage to primary organs and satisfactory biocompatibility were observed in the murine model. Collectively, these findings highlight the therapeutic potential of this MPDA-based platform for controlling bacterial infection and accelerating wound healing.

Copolymers of starch, a sustainable template for biomedical applications: A review.

The outstanding versatility of starch offers a source of inspiration for the development of high-performance-value-added biomaterials for the biomedical field, including drug delivery, tissue engineering and diagnostic imaging. This is because starch-based materials can be tailored to specific applications via facile grafting or other chemistries, introducing specific substituents, with starch being effectively the "template" used in all the chemical transformations discussed in this review. A considerable effort has been carried out to obtain specific tailored starch-based grafted polymers, taking advantage of its biocompatibility and biodegradability with appealing sustainability considerations. The aim of this review is to critically explore the latest research that use grafting chemistries on starch for the synthesis of products for biomedical applications. An effort is made in reviewing the literature that proposes synthetic "greener" approaches, the use of enzymes and their immobilized analogues and alternative solvent systems, including water emulsions, ionic liquids and supercritical CO2.

Microstructure and properties of thermomechanically processed chitosan citrate-based materials.

The traditional solvent casting method for preparing chitosan-based materials has limited productivity relative to the productivity of thermomechanical processing. Consequently, the thermomechanical processing technique was evaluated as a way to increase chitosan production. The role of citric acid (CA) as a destructuring and crosslinking agent during such processing was examined. SEM images revealed robust fibers that were associated with a superior mechanical strength (145%), which were produced after thermomechanical processing of chitosan in the presence of CA. Based on articles reviewed, this is the first time that this structure has been closely observed in the microstructure of chitosan-based materials. FTIR and XRD characterization showed the occurrence of chemical crosslinking and the successful destructuring of chitosan powder by CA during processing. Compared to acetic acid, the use of CA led to the development of materials with a homogeneous morphology and good physicochemical and mechanical properties that are suitable for biomedical applications.

Multivalent Supramolecular Assembly Based on a Triphenylamine Derivative for Near-Infrared Lysosome Targeted Imaging.

Near-infrared (NIR) targeted cell imaging has become a research hotspot due to the advantages of deeper tissue penetration, minimal interference from the background signals, and lower light damage. Herein, we report a multivalent supramolecular aggregate with NIR fluorescence emission, which was fabricated from triphenylamine derivatives (TPAs), cucurbit[8]uril (CB[8]), Si-rhodamine (SiR), and hyaluronic acid (HA). Interestingly, possessing a rigid luminescent core and cationic phenylpyridinium units linked by flexible alkyl chains, the tripaddle hexacationic TPA could bind with CB[8] at a 2:3 stoichiometric ratio to form a network-like multivalent assembly with enhanced red luminescence. Such organic two-dimensional network-like aggregate further co-assembled with the energy acceptor SiR and cancer cell targeting agent HA, leading to nanoparticles with NIR emission at 675 nm via an intermolecular energy transfer pathway. Furthermore, the obtained multivalent supramolecular aggregate was successfully applied in lysosome targeted imaging toward A549 cancer cells, which provides a convenient strategy for NIR targeted cell imaging.

Efficient Magnetic Nanocatalyst-Induced Chemo- and Ferroptosis Synergistic Cancer Therapy in Combination with T1-T2 Dual-Mode Magnetic Resonance Imaging Through Doxorubicin Delivery.

Excessive iron ions in cancer cells can catalyze H2O2 into highly toxic •OH and then promote the generation of reactive oxygen species (ROS), inducing cancer ferroptosis. However, the efficacy of the ferroptosis catalyst is still insufficient because of low Fe(II) release, which severely limited its application in clinic. Herein, we developed a novel magnetic nanocatalyst for MRI-guided chemo- and ferroptosis synergistic cancer therapies through iRGD-PEG-ss-PEG-modified gadolinium engineering magnetic iron oxide-loaded Dox (ipGdIO-Dox). The introduction of the gadolinium compound disturbed the structure of ipGdIO-Dox, making the magnetic nanocatalyst be more sensitive to weak acid. When ipGdIO-Dox entered into cancer cells, abundant Fe(II) ions were released and then catalyzed H2O2 into highly toxic OH•, which would elevate cellular oxidative stress to damage mitochondria and cell membranes and induce cancer ferroptosis. In addition, the iRGD-PEG-ss-PEG chain coated onto the nanoplatform was also broken by high expression of GSH, and then, the Dox was released. This process not only effectively inhibited DNA replication but also further activated cellular ROS, making the nanoplatform achieve stronger anticancer ability. Besides, the systemic delivery of ipGdIO-Dox significantly enhanced the T1- and T2-weighted MRI signal of the tumor, endowing accurate diagnostic capability for tumor recognition. Therefore, ipGdIO-Dox might be a promising candidate for developing an MRI-guided chemo- and ferroptosis synergistic theranostic system.