Molecularly Imprinted Macroporous Hydrogel Promotes Bone Regeneration via Osteogenic Induction and Osteoclastic Inhibition.

Macroporous hydrogels offer physical supportive spaces and bio-instructive environment for the seeded cells, where cell-scaffold interactions directly influence cell fates and subsequently affect tissue regeneration post-implantation. Effectively modifying bioactive motifs at the inner pore surface provides appropriate niches for cell-scaffold interactions. A molecular imprinting method and sacrificial templates are introduced to prepare inner pore surface modification in the macroporous hydrogels. In detail, acrylated bisphosphonates (Ac-BPs) chelating to templates (CaCO3 particles) are anchored on the inner pore surface of the methacrylated gelatin (GelMA)-methacrylated hyaluronic acid (HAMA)-poly (ethylene glycol) diacrylate (PEGDA) macroporous hydrogel (GHP) to form a functional hydrogel scaffold (GHP-int-BP). GHP-int-BP, but not GHP, effectively crafts artificial cell niches to substantially alter cell fates, including osteogenic induction and osteoclastic inhibition, and promote in situ bone regeneration. These findings highlight that molecular imprinting on the inner pore surface in the hydrogel efficiently creates orthogonally additive bio-instructive scaffolds for bone regeneration.

Mussel shell-derived pro-regenerative scaffold with conductive porous multi-scale-patterned microenvironment for spinal cord injury repair.

It is well-established that multi-scale porous scaffolds can guide axonal growth and facilitate functional restoration after spinal cord injury (SCI). In this study, we developed a novel mussel shell-inspired conductive scaffold for SCI repair with ease of production, multi-scale porous structure, high flexibility, and excellent biocompatibility. By utilizing the reducing properties of polydopamine, non-conductive graphene oxide (GO) was converted into conductive reduced graphene oxide (rGO) and crosslinkedin situwithin the mussel shells.In vitroexperiments confirmed that this multi-scale porous Shell@PDA-GO could serve as structural cues for enhancing cell adhesion, differentiation, and maturation, as well as promoting the electrophysiological development of hippocampal neurons. After transplantation at the injury sites, the Shell@PDA-GO provided a pro-regenerative microenvironment, promoting endogenous neurogenesis, triggering neovascularization, and relieving glial fibrosis formation. Interestingly, the Shell@PDA-GO could induce the release of endogenous growth factors (NGF and NT-3), resulting in the complete regeneration of nerve fibers at 12 weeks. This work provides a feasible strategy for the exploration of conductive multi-scale patterned scaffold to repair SCI.

A rapid interactive chitosan-based medium with antioxidant and pro-vascularization properties for infected burn wound healing.

Large-pore hydrogels are better suited to meet the management needs of nutrient transportation and gas exchange between infected burn wounds and normal tissues. However, better construction strategies are required to balance the pore size and mechanical strength of hydrogels to construct a faster substance/gas interaction medium between tissues. Herein, we developed spongy large pore size hydrogel (CS-TA@Lys) with good mechanical properties using a simple ice crystal-assisted method based on chitosan (CS), incorporating tannic acid (TA) and ε-polylysine (Lys). A large-pore and mechanically robust hydrogel medium was constructed based on hydrogen bonding between CS molecules. On this basis, a pro-restorative functional platform with antioxidation and pro-vascularization was constructed using TA and Lys. In vitro experiments displayed that the CS-TA@Lys hydrogel possessed favorable mechanical properties and fast interaction performances. In addition, the CS-TA@Lys hydrogel possessed the capacity to remove intra/extracellular reactive oxygen species (ROS) and possessed antimicrobial and pro-angiogenic properties. In vivo experiments displayed that the CS-TA@Lys hydrogel inhibited wound inflammation and promoted wound vascularization. In addition, the CS-TA@Lys hydrogel showed the potential for rapid hemostasis. This study provides a potential functional wound dressing with rapid interaction properties for skin wound repair.

3D sponge loaded with cisplatin-CS-calcium alginate MPs utilized as a void-filling prosthesis for the efficient postoperative prevention of tumor recurrence and metastasis.

Intraoperative bleeding is a pivotal factor in the initiation of early recurrence and tumor metastasis following breast cancer excision. Distinct advantages are conferred upon postoperative breast cancer treatment through the utilization of locally administered implant therapies. This study devised a novel 3D sponge implant containing cisplatin-loaded chitosan-calcium alginate MPs capable of exerting combined chemotherapy and hemostasis effects. This innovative local drug-delivery implant absorbed blood and residual tumor cells post-tumor resection. Furthermore, the cisplatin-loaded chitosan-calcium alginate MPs sustainably targeted and eliminated cancer cells, thereby diminishing the risk of local recurrence and distant metastasis. This hydrogel material can also contribute to breast reconstruction, indicating the potential application of the 3D sponge in drug delivery for breast cancer treatment.

A cigarette filter-derived biomimetic cardiac niche for myocardial infarction repair.

Cell implantation offers an appealing avenue for heart repair after myocardial infarction (MI). Nevertheless, the implanted cells are subjected to the aberrant myocardial niche, which inhibits cell survival and maturation, posing significant challenges to the ultimate therapeutic outcome. The functional cardiac patches (CPs) have been proved to construct an elastic conductive, antioxidative, and angiogenic microenvironment for rectifying the aberrant microenvironment of the infarcted myocardium. More importantly, inducing implanted cardiomyocytes (CMs) adapted to the anisotropic arrangement of myocardial tissue by bioengineered structural cues within CPs are more conducive to MI repair. Herein, a functional Cig/(TA-Cu) CP served as biomimetic cardiac niche was fabricated based on structural anisotropic cigarette filter by modifying with tannic acid (TA)-chelated Cu2+ (TA-Cu complex) via a green method. This CP possessed microstructural anisotropy, electrical conductivity and mechanical properties similar to natural myocardium, which could promote elongation, orientation, maturation, and functionalization of CMs. Besides, the Cig/(TA-Cu) CP could efficiently scavenge reactive oxygen species, reduce CM apoptosis, ultimately facilitating myocardial electrical integration, promoting vascular regeneration and improving cardiac function. Together, our study introduces a functional CP that integrates multimodal cues to create a biomimetic cardiac niche and provides an effective strategy for cardiac repair.

Zwitterionic Conductive Hydrogel-Based Nerve Guidance Conduit Promotes Peripheral Nerve Regeneration in Rats.

In recent years, conductive biomaterials have been widely used to enhance peripheral nerve regeneration. However, most biomaterials use electronic conductors to increase the conductivity of materials. As information carriers, electronic conductors always transmit discontinuous electrical signals, while biological systems essentially transmit continuous signals through ions. Herein, an ion-based conductive hydrogel was fabricated by simple copolymerization of the zwitterionic monomer sulfobetin methacrylate and hydroxyethyl methacrylate. Benefiting from the excellent mechanical stability, suitable electrical conductivity, and good cytocompatibility of the zwitterionic hydrogel, the Schwann cells cultured on the hydrogel could grow and proliferate better, and dorsal root ganglian had an increased neurite length. The zwitterionic hydrogel-based nerve guidance conduits were then implanted into a 10 mm sciatic nerve defect model in rats. Morphological analysis and electrophysiological data showed that the grafts achieved a regeneration effect close to that of the autologous nerve. Overall, our developed zwitterionic hydrogel facilitates efficient and efficacious peripheral nerve regeneration by mimicking the electrical and mechanical properties of the extracellular matrix and creating a suitable regeneration microenvironment, providing a new material reserve for the repair of peripheral nerve injury.

Ammonium Persulfate-Loaded Carboxylic Gelatin-Methacrylate Nanoparticles Promote Cardiac Repair by Activating Epicardial Epithelial-Mesenchymal Transition via Autophagy and the mTOR Pathway.

Restoring damaged myocardial tissue with therapeutic exogenous cells still has some limitations, such as immunological rejection, immature cardiac properties, risk of tumorigenicity, and a low cell survival rate in the ischemic myocardium microenvironment. Activating the endogenous stem cells with functional biomaterials might overcome these limitations. Research has highlighted the multiple differentiation potential of epicardial cells via epithelial-mesenchymal transition (EMT) in both heart development and cardiac regeneration. In our previous research, a carboxylic gelatin-methacrylate (carbox-GelMA) nanoparticle (NP) was fabricated to carry ammonium persulfate (APS), and APS-loaded carbox-GelMA NPs (NPs/APS) could drive the EMT of MCF-7 cells in vitro and promote cancer cell migration and invasion in vivo. The present study explored the roles of functional NPs/APS in the EMT of Wilms' tumor 1-positive (WT1+) epicardial cells and in the repair of myocardial infarction (MI). The WT1+ epicardial cells transformed into endothelial-like cells after being treated with NPs/APS in vitro, and the cardiac functions were improved significantly after injecting NPs/APS into the infarcted hearts in vivo. Furthermore, simultaneous activation of both autophagy and the mTOR pathway was confirmed during the NPs/APS-induced EMT process in WT1+ epicardial cells. Together, this study highlights the function of NPs/APS in the repair of MI.

A STING pathway-activatable contrast agent for MRI-guided tumor immunoferroptosis synergistic therapy.

The immunotherapy efficiency of stimulator of interferon genes (STING)-activatable drugs (e.g., 7-ethyl-10-hydroxycamptothecin, SN38) is limited by their non-specificity to tumor cells and the slow excretion of the DNA-containing exosomes from the treated cancer cells. The efficacy of tumor ferroptosis therapy is always limited by the elimination of lipid peroxides (LPO) by the pathways of glutathione peroxidase 4 (GPX4), dihydroorotate dehydrogenase (DHODH) and ferroptosis suppressor protein 1(FSP1). To solve these problems, in this study, we developed a STING pathway-activatable contrast agent (i.e., FeGd-HN@TA-Fe2+-SN38 nanoparticles) for magnetic resonance imaging (MRI)-guided tumor immunoferroptosis synergistic therapy. The remarkable in vivo MRI performance of FeGd-HN@TA-Fe2+-SN38 is attributed to its high accumulation at tumor location, the high relaxivities of FeGd-HN core, and the pH-sensitive TA-Fe2+-SN38 layer. The effectiveness and biosafety of the immunoferroptosis synergistic therapy induced by FeGd-HN@TA-Fe2+-SN38 are demonstrated by the in vivo investigations on the 4T1 tumor-bearing mice. The mechanisms of in vivo immunoferroptosis synergistic therapy by FeGd-HN@TA-Fe2+-SN38 are demonstrated by measurements of in vivo ROS, LPO, GPX4 and SLC7A11 levels, the intratumor matured DCs and CD8+ T cells, the protein expresion of STING and IRF-3, and the secretion of IFN-ß and IFN-γ.

Flexible Conductive Decellularized Fish Skin Matrix as a Functional Scaffold for Myocardial Infarction Repair.

Engineering cardiac patches are proven to be effective in myocardial infarction (MI) repair, but it is still a tricky problem in tissue engineering to construct a scaffold with good biocompatibility, suitable mechanical properties, and solid structure. Herein, decellularized fish skin matrix is utilized with good biocompatibility to prepare a flexible conductive cardiac patch through polymerization of polydopamine (PDA) and polypyrrole (PPy). Compared with single modification, the double modification strategy facilitated the efficiency of pyrrole polymerization, so that the patch conductivity is improved. According to the results of experiments in vivo and in vitro, the scaffold can promote the maturation and functionalization of cardiomyocytes (CMs). It can also reduce the inflammatory response, increase local microcirculation, and reconstruct the conductive microenvironment in infarcted myocardia, thus improving the cardiac function of MI rats. In addition, the excellent flexibility of the scaffold, which enables it to be implanted in vivo through "folding-delivering-re-stretehing" pathway, provides the possibility of microoperation under endoscope, which avoids the secondary damage to myocardium by traditional thoracotomy for implantation surgery.

A Core-Shell Nanoreinforced Ion-Conductive Implantable Hydrogel Bioelectronic Patch with High Sensitivity and Bioactivity for Real-Time Synchronous Heart Monitoring and Repairing.

To achieve synchronous repair and real-time monitoring the infarcted myocardium based on an integrated ion-conductive hydrogel patch is challenging yet intriguing. Herein, a novel synthetic strategy is reported based on core-shell-structured curcumin-nanocomposite-reinforced ion-conductive hydrogel for synchronous heart electrophysiological signal monitoring and infarcted heart repair. The nanoreinforcement and multisite cross-linking of bioactive curcumin nanoparticles enable well elasticity with negligible hysteresis, implantability, ultrahigh mechanoelectrical sensitivity (37 ms), and reliable sensing capacity (over 3000 cycles) for the nanoreinforced hydrogel. Results of in vitro and in vivo experiments demonstrate that such solely physical microenvironment of electrophysiological and biomechanical characteristics combining with the role of bioactive curcumin exert the synchronous benefit of regulating inflammatory microenvironment, promoting angiogenesis, and reducing myocardial fibrosis for effective myocardial infarction (MI) repair. Especially, the hydrogel sensors offer the access for achieving accurate acquisition of cardiac signals, thus monitoring the whole MI healing process. This novel bioactive and electrophysiological-sensing ion-conductive hydrogel cardiac patch highlights a versatile strategy promising for synchronous integration of in vivo real-time monitoring the MI status and excellent MI repair performance.

Tumor-Generated Reactive Oxygen Species Storm for High-Performance Ferroptosis Therapy.

Ferroptosis therapy (FT) efficacy of tumors suffers from a relatively low concentration of Fenton agents, limited hydrogen peroxide (H2O2) content, and insufficient acidity in the tumor environment (TME), which are unfavorable for reactive oxygen species (ROS) generation based on Fenton or Fenton-like reactions. The glutathione (GSH) overexpression in TME can scavenge ROS and abate the FT performance. In this study, a strategy of ROS storm generation specifically initiated by the TME and our developed nanoplatforms (TAF-HMON-CuP@PPDG) is proposed for high-performance FT of tumors. The GSH in the TME initiates HMON degradation, resulting in tamoxifen (TAF) and copper peroxide (CuP) release from TAF3-HMON-CuP3@PPDG. The released TAF leads to enhanced acidification within tumor cells, which reacts with the released CuP producing Cu2+ and H2O2. The Fenton-like reaction between Cu2+ and H2O2 generates ROS and Cu+, and that between Cu+ and H2O2 generates ROS and Cu2+, forming a cyclic catalysis effect. Cu2+ reacts with GSH to generate Cu+ and GSSG. The increased acidification by TAF can accelerate the Fenton-like reaction between Cu+ and H2O2. The GSH consumption decreases the glutathione peroxidase 4 (GPX4) expression. All of the above reactions generate a ROS storm in tumor cells for high-performance FT, which is demonstrated in cancer cells and tumor-bearing mice.

Cardiac-Adaptive Conductive Hydrogel Patch Enabling Construction of Mechanical-Electrical Anisotropic Microenvironment for Heart Repair.

The biomimetic construction of a microstructural-mechanical-electrical anisotropic microenvironment adaptive to the native cardiac tissue is essential to repair myocardial infarction (MI). Inspired by the 3D anisotropic characteristic of the natural fish swim bladder (FSB), a novel flexible, anisotropic, and conductive hydrogel was developed for tissue-specific adaptation to the anisotropic structural, conductive, and mechanical features of the native cardiac extracellular matrix. The results revealed that the originally stiff, homogeneous FSB film was tailored to a highly flexible anisotropic hydrogel, enabling its potential as a functional engineered cardiac patch (ECP). In vitro and in vivo experiments demonstrated the enhanced electrophysiological activity, maturation, elongation, and orientation of cardiomyocytes (CMs), and marked MI repair performance with reduced CM apoptosis and myocardial fibrosis, thereby promoting cell retention, myogenesis, and vascularization, as well as improving electrical integration. Our findings offer a potential strategy for functional ECP and provides a novel strategy to bionically simulate the complex cardiac repair environment.

An injectable elastic hydrogel crosslinked with curcumin-gelatin nanoparticles as a multifunctional dressing for the rapid repair of bacterially infected wounds.

Injectable self-healing hydrogel dressings with excellent elasticity and multifunctional repair effects have been in high demand in wound healing applications, while maintaining stable elasticity in injectable multifunctional hydrogel dressings is still a challenge. Based on carboxymethyl chitosan (CMCS), curcumin-gelatin nanoparticles (CG NPs), and sodium alginate oxide (OSA), we developed a double-crosslinking injectable elastic self-healing hydrogel without any chemical cross-linking agent as a multifunctional wound healing dressing. CG NPs were more stable than pure curcumin (Cur) nanoparticles and could regulate the cross-linking of injectable hydrogels for high elasticity and rapid self-healing. We found that the CG NPs endowed the injectable hydrogel with good anti-inflammatory, antibacterial, and reactive oxygen scavenging activities and could significantly shorten the wound healing time in infected full-thickness skin defect rats by promoting the polarization of M2-type macrophages, reducing oxidative damage, accelerating collagen deposition, enhancing granulation formation, and elevating angiogenesis. Taken together, the tunable elastic injectable hydrogel dressing exhibited a long-term service life with sustained repair function and can be taken as an optimal candidate for bacteria-infected wound healing.

Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications.

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and regenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, and inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regenerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), including advances in their preparation, functionality, potential applications and future challenges. We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Improved cancer immunotherapy strategies by nanomedicine.

Cancer immunotherapy agents fight cancer via immune system stimulation and have made significant advances in minimizing side effects and prolonging the survival of patients with solid tumors. However, major limitations still exist in cancer immunotherapy, including the inefficiency of immune response stimulation in specific cancer types, therapy resistance caused by the tumor microenvironment (TME), toxicities by the immune imbalance, and short lifetime of stimulator of interferon genes (STING) agonist. Recent advances in nanomedicine have shown significant potential in overcoming the obstacles of cancer immunotherapy. Several nanoscale agents have been reported for cancer immunotherapy, including nanoscale cancer vaccines impacting the STING pathway, nanomaterials reprogramming TME, nano-agents triggering immune response with immune checkpoint inhibitor synergy, ferroptosis-mediated and indoleamine-2,3-dioxygenase immunosuppression-mediated cancer immunotherapy, and nanomedicine-meditated chimeric antigen receptor-T-cell therapy. Herein, we summarize the major advances and innovations in nanomedicine-based cancer immunotherapy, and outline the opportunities and challenges to integrate more advanced nanomaterials into cancer immunotherapy. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Highly Stretchable and Biocompatible Wrinkled Nanoclay-Composite Hydrogel With Enhanced Sensing Capability for Precise Detection of Myocardial Infarction.

It is challenging to balance high biocompability with good mechanical-electrical sensing performance, especially when triggering inflammatory stress response after in vivo implantation. Herein, a bioinspired wrinkle-reinforced adaptive nanoclay-interlocked soft strain-sensor based on a highly stretchable and elastic ionic-conductive hydrogel is reported. This novel nanoclay-composite hydrogel exhibits excellent tensile properties and high sensing capacity with steady and reliable sensing performance due to the structural-mechanical-electrical integrity of the nanoclay crosslinked and nano-reinforced interpenetrating network. The incorporation of amphiphilic ions provides the hydrogel with significant protein resistance, reducing its non-specific adsorption to proteins upon implantation, improving its biosafety as an implanted device, and maintaining the authenticity of the sensing results. Based on the revealed sensing enhanced mechanism based on hierarchical ordered structures as a proof-of-concept application, this hydrogel sensor is demonstrated to be able to accurately localize the region where myocardial infarction occurs and may become a novel strategy for real-time monitoring of pathological changes in heart disease.

A smart adhesive Janus hydrogel for non-invasive cardiac repair and tissue adhesion prevention.

Multifunctional hydrogel with asymmetric and reversible adhesion characteristics is essential to handle the obstructions towards bioapplications of trauma removal and postoperative tissue synechia. Herein, we developed a responsively reversible and asymmetrically adhesive Janus hydrogel that enables on-demand stimuli-triggered detachment for efficient myocardial infarction (MI) repair, and synchronously prevents tissue synechia and inflammatory intrusion after surgery. In contrast with most irreversibly and hard-to-removable adhesives, this Janus hydrogel exhibited a reversible adhesion capability and can be noninvasively detached on-demand just by slight biologics. It is interesting that the adhesion behaves exhibited a molecularly encoded adhesion-adaptive stiffening feature similar to the self-protective stress-strain effect of biological tissues. In vitro and in vivo experiments demonstrated that Janus hydrogel can promote the maturation and functions of cardiomyocytes, and facilitate MI repair by reducing oxidative damage and inflammatory response, reconstructing electrical conduction and blood supply in infarcted area. Furthermore, no secondary injury and tissue synechia were triggered after transplantation of Janus hydrogel. This smart Janus hydrogel reported herein offers a potential strategy for clinically transformable cardiac patch and anti-postoperative tissue synechia barrier.

Tumor-specific cyclic amplification of oxidative stress by disulfide-loaded fluoropolymer nanogels.

Amplification of intracellular oxidative stress has been found to be an effective strategy to induce cancer cell death. Herein, the effect of a disulfide, 2,2'-dithiobis(5-aminopyridine) (BAPS), is revealed on depleting glutathione (GSH) circularly and generating superoxide anion (O2•-) spontaneously to manipulate intracellular redox homeostasis. Thus, BAPS is able to work as an oxidative stress amplifier in cancer cells with high GSH concentrations and kill them efficiently. Moreover, leveraging a new class of water-soluble fluoropolymers poly(N-(2-((2,2,2-trifluoroethyl)sulfonyl)ethyl)acrylamide) (PFSNM), BAPS, together with oxygen, can be effectively delivered into hypoxic tumor cells through circulation and significantly inhibit the tumor growth. Therefore, BAPS-loaded PFSNM is an oxidative regulation nanosystem with remarkable therapeutic efficacy for chemodynamic therapy.

Elastic and Conductive Melanin/Poly(Vinyl Alcohol) Composite Hydrogel for Enhancing Repair Effect on Myocardial Infarction.

Heart failure caused by acute myocardial infarction (MI) still remains the main cause of death worldwide. Development of conductive hydrogels provided a promising approach for the treatment of myocardial infarction. However, the therapeutic potential of these hydrogels is still limited by material toxicity or low conductivity. The latter directly affects the coupling and the propagation of electrical signals between cells. Here, a functional conductive hydrogel by combining hydrophilic and biocompatible poly(vinyl alcohol) (PVA) with conductive melanin nanoparticles under physical crosslinking conditions is prepared. The composite hydrogels prepared by a facile fabrication process of five freeze/thaw cycles possessed satisfying mechanical properties and conductivity close to those of the natural heart. The physical properties and biocompatibility are evaluated in vitro experiments, showing that the introduction of melanin particles successfully improved the elasticity, conductivity, and cell adhesion of PVA hydrogel. In vivo, the composite hydrogels can enhance the cardiac repair effect by reducing MI area, slowing down ventricular wall thinning, and promoting the vascularization of infarct area in MI rat model. It is believed that the melanin/PVA composite hydrogel may be a suitable candidate material for MI repair.

Cycloacceleration of Reactive Oxygen Species Generation Based on Exceedingly Small Magnetic Iron Oxide Nanoparticles for Tumor Ferroptosis Therapy.

Because of the insufficiency of hydrogen peroxide, the relatively low rate of Fenton reaction, and the active glutathione (GSH) peroxidase 4 (GPX4) in tumor cells, it is difficult to achieve a desirable efficacy of ferroptosis therapy (FT) for tumors based on nanomaterials. Inspired by the concept of "cyclotron" in physics, in this study, a new concept of cycloacceleration of reactive oxygen species (ROS) generation in tumor cells to realize high-performance FT of tumors is proposed. Typically, a magnetic resonance imaging (MRI) contrast agent of dotted core-shell Fe3 O4 /Gd2 O3 hybrid nanoparticles (FGNPs) is prepared based on exceedingly small magnetic iron oxide nanoparticles (ES-MIONs). Sorafenib (SFN) is loaded and poly(ethylene glycol) methyl ether-poly(propylene sulfide)-NH2 (mPEG-PPS-NH2 ) is grafted on the surface of FGNP to generate SA-SFN-FGNP via self-assembly. The results of in vitro and in vivo demonstrate SA-SFN-FGNP can work with the acidic tumor microenvironment and endosomal conditions, Fenton reaction and system XC - , and generate cyclic reactions in tumor cells, resulting in specific cycloacceleration of ROS generation for high-performance FT of tumors. The very high longitudinal relaxivity (r1 , 33.43 mM-1 s-1 , 3.0 T) makes sure that the SA-SFN-FGNP can be used for MRI-guided FT of tumors.