Recurrent Inhibition Research Articles

3D printed hydrogel scaffolds combining glutathione depletion-induced ferroptosis and photothermia-augmented chemodynamic therapy for efficiently inhibiting postoperative tumor recurrence

Surgical resection to achieve tumor-free margins represents a difficult clinical scenario for patients with hepatocellular carcinoma. While post-surgical treatments such as chemotherapy and radiotherapy can decrease the risk of cancer recurrence and metastasis, growing concerns about the complications and side effects have promoted the development of implantable systems for locoregional treatment. Herein, 3D printed hydrogel scaffolds (designed as Gel-SA-CuO) were developed by incorporating one agent with multifunctional performance into implantable devices to simplify the fabrication process for efficiently inhibiting postoperative tumor recurrence. CuO nanoparticles can be effectively controlled and sustained released during the biodegradation of hydrogel scaffolds. Notably, the released CuO nanoparticles not only function as the reservoir for releasing Cu2+ to produce intracellular reactive oxygen species (ROS) but also serve as photothermal agent to generate heat. Remarkably, the heat generated by photothermal conversion of CuO nanoparticles further promotes the efficiency of Fenton-like reaction. Additionally, ferroptosis can be induced through Cu2+-mediated GSH depletion via the inactivation of GPX4. By implanting hydrogel scaffolds in the resection site, efficient inhibition of tumor recurrence after primary resection can be achieved in vivo. Therefore, this study may pave the way for the development of advanced multifunctional implantable platform for eliminating postoperative relapsable cancers.Graphical

Internally generated population activity in cortical networks hinders information transmission.

How neuronal variability affects sensory coding is a central question in systems neuroscience, often with complex and model-dependent answers. Many studies explore population models with a parametric structure for response tuning and variability, preventing an analysis of how synaptic circuitry establishes neural codes. We study stimulus coding in networks of spiking neuron models with spatially ordered excitatory and inhibitory connectivity. The wiring structure is capable of producing rich population-wide shared neuronal variability that agrees with many features of recorded cortical activity. While both the spatial scales of feedforward and recurrent projections strongly affect noise correlations, only recurrent projections, and in particular inhibitory projections, can introduce correlations that limit the stimulus information available to a decoder. Using a spatial neural field model, we relate the recurrent circuit conditions for information limiting noise correlations to how recurrent excitation and inhibition can form spatiotemporal patterns of population-wide activity.

Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment

At present, the 10-year survival rate of patients with pancreatic cancer is still less than 4%, mainly due to the high cancer recurrence rate caused by incomplete surgery and lack of effective postoperative adjuvant treatment. Systemic chemotherapy remains the only choice for patients after surgery; however, it is accompanied by off-target effects and server systemic toxicity. Herein, we proposed a biodegradable microdevice for local sustained drug delivery and postoperative pancreatic cancer treatment as an alternative and safe option. Biodegradable poly(l-lactic-co-glycolic acid) (P(L)LGA) was developed as the matrix material, gemcitabine hydrochloride (GEM·HCl) was chosen as the therapeutic drug and polyethylene glycol (PEG) was employed as the drug release-controlled regulator. Through adjusting the amount and molecular weight of PEG, the controllable degradation of matrix and the sustained release of GEM·HCl were obtained, thus overcoming the unstable drug release properties of traditional microdevices. The drug release mechanism of microdevice and the regulating action of PEG were studied in detail. More importantly, in the treatment of the postoperative recurrence model of subcutaneous pancreatic tumor in mice, the microdevice showed effective inhibition of postoperative in situ recurrences of pancreatic tumors with excellent biosafety and minimum systemic toxicity. The microdevice developed in this study provides an option for postoperative adjuvant pancreatic treatment, and greatly broadens the application prospects of traditional chemotherapy drugs.

Two-Stage Targeted Bismuthene-Based Composite Nanosystem for Multimodal Imaging Guided Enhanced Hyperthermia and Inhibition of Tumor Recurrence

A key challenge for nanomedicines in clinical application is to reduce the dose while achieving excellent efficacy, which has attracted extensive attention in dose toxicity and potential risks. It is thus necessary to reasonably design nanomedicine with high-efficiency targeting and accumulation. Here, we designed and synthesized a tetragonal bismuthene-based "all-in-one" composite nanosystem (TPP-Bi@PDA@CP) with two-stage targeting, multimodal imaging, photothermal therapy, and immune enhancement functions. Through the elaborate design of its structure, the composite nanosystem possesses multiple properties including (i) two-stage targeting function of hepatoma cells and mitochondria [the aggregation at the tumor site is 2.63-fold higher than that of traditional enhanced permeability and retention (EPR) effect]; (ii) computed tomography (CT) contrast-enhancement efficiency as high as ∼51.8 HU mL mg-1 (3.16-fold that of the clinically available iopromide); (iii) ultrahigh photothermal conversion efficiency (52.3%, 808 nm), promising photothermal therapy (PTT), and high-contrast infrared thermal (IRT)/photoacoustic (PA) imaging of tumor; (iv) benefitting from the two-stage targeting function and excellent photothermal conversion ability, the dose used in this strategy is one of the lowest doses in hyperthermia (the inhibition rate of tumor cells was 50% at a dose of 15 μg mL-1 and 75% at a dose of 25 μg mL-1); (v) the compound polysaccharide (CP) shell with hepatoma cell targeting and immune enhancement functions effectively inhibited the recurrence of tumor. Therefore, our work reduces the dose toxicity and potential risk of nanomedicines and highlights the great potential as an all-in-one theranostic nanoplatform for two-stage targeting, integrated diagnostic imaging, photothermal therapy, and inhibition of tumor recurrence.

Immunogenic hydrogel toolkit disturbing residual tumor “seeds” and pre-metastatic “soil” for inhibition of postoperative tumor recurrence and metastasis

Tumor recurrence and metastasis is the leading cause of mortality for postoperative breast cancer patients. However, chemotherapy intervention after surgery is often unsatisfactory, because residual microtumors are difficult to target and require frequent administration. Here, an all-in-one and once-for-all drug depot based on in situ-formed hydrogel was applied to fit the irregular surgical trauma, and enable direct contact with residual tumors and sustained drug release. Our immunological analysis after resection of orthotopic breast tumor revealed that postsurgical activation of CXCR4–CXCL12 signal exacerbated the immunosuppression and correlated with adaptive upregulation of PD-L1 in recurrent tumors. Thus, a multifunctional hydrogel toolkit was developed integrating strategies of CXCR4 inhibition, immunogenicity activation and PD-L1 blockade. Our results showed that the hydrogel toolkit not only exerted local effect on inhibiting residual tumor cell “seeds” but also resulted in abscopal effect on disturbing pre-metastatic “soil”. Furthermore, vaccine-like effect and durable antitumor memory were generated, which resisted a secondary tumor rechallenge in 100% cured mice. Strikingly, one single dose of such modality was able to eradicate recurrent tumors, completely prevent pulmonary metastasis and minimize off-target toxicity, thus providing an effective option for postoperative intervention.

Sparse balance: Excitatory-inhibitory networks with small bias currents and broadly distributed synaptic weights.

Cortical circuits generate excitatory currents that must be cancelled by strong inhibition to assure stability. The resulting excitatory-inhibitory (E-I) balance can generate spontaneous irregular activity but, in standard balanced E-I models, this requires that an extremely strong feedforward bias current be included along with the recurrent excitation and inhibition. The absence of experimental evidence for such large bias currents inspired us to examine an alternative regime that exhibits asynchronous activity without requiring unrealistically large feedforward input. In these networks, irregular spontaneous activity is supported by a continually changing sparse set of neurons. To support this activity, synaptic strengths must be drawn from high-variance distributions. Unlike standard balanced networks, these sparse balance networks exhibit robust nonlinear responses to uniform inputs and non-Gaussian input statistics. Interestingly, the speed, not the size, of synaptic fluctuations dictates the degree of sparsity in the model. In addition to simulations, we provide a mean-field analysis to illustrate the properties of these networks.

Inhibition of post-surgery tumour recurrence via a sprayable chemo-immunotherapy gel releasing PD-L1 antibody and platelet-derived small EVs

BackgroundMelanoma is the most serious type of skin cancer, and surgery is an effective method to treat melanoma. Unfortunately, local residual micro-infiltrated tumour cells and systemic circulating tumour cells (CTCs) are significant causes of treatment failure, leading to tumour recurrence and metastasis.MethodsSmall EVs were isolated from platelets by differential centrifugation, and doxorubicin-loaded small EVs (PexD) was prepared by mixing small EVs with doxorubicin (DOX). PexD and an anti-PD-L1 monoclonal antibody (aPD-L1) were co-encapsulated in fibrin gel. The synergistic antitumour efficacy of the gel containing PexD and aPD-L1 was assessed both in vitro and in vivo.ResultsHerein, we developed an in situ-formed bioresponsive gel combined with chemoimmunotherapeutic agents as a drug reservoir that could effectively inhibit both local tumour recurrence and tumour metastasis. In comparison with a DOX solution, PexD could better bind to tumour cells, induce more tumour immunogenic cell death (ICD) and promote a stronger antitumour immune response. PexD could enter the blood circulation through damaged blood vessels to track and eliminate CTCs. The concurrent release of aPD-L1 at the tumour site could impair the PD-1/PD-L1 pathway and restore the tumour-killing effect of cytotoxic T cells. This chemoimmunotherapeutic strategy triggered relatively strong T cell immune responses, significantly improving the tumour immune microenvironment.ConclusionOur findings indicated that the immunotherapeutic fibrin gel could “awaken” the host innate immune system to inhibit both local tumour recurrence post-surgery and metastatic potential, thus, it could serve as a promising approach to prevent tumour recurrence.Graphical

Nanocomposite multifunctional hydrogel for suppressing osteosarcoma recurrence and enhancing bone regeneration

Osteosarcoma (OS) is the most prevalent primary malignancy of bone. Inhibition of OS recurrence and subsequent bone formation after surgery remains a challenge for decades. Innovative biomaterials with the dual function of tumor therapy and bone regeneration have emerged as a promising strategy for OS treatment. We developed a bioactive nanoparticle (MDA-NPs) composed of magnesium oxide nanoparticle (M-NPs) core and 2-Aminoethyl methacrylate (2-AM) grafted polydopamine (PDAM) shell. The phosphonate modified methacrylamide chitosan (CMP) and polyacrylamide (PAM) were prepared to form a pre-gel, and then a series of MDA-NPs nanocomposite with 0 mg/mL, 0.5 mg/mL, 2.5 mg/mL, 5 mg/mL, and 10 mg/mL were incorporated and coded as CMP@PAM, 0.5NP/CMP@PAM, 2.5NP/CMP@PAM, 5NP/CMP@PAM, 10NP/CMP@PAM, respectively. We found that 5NP/CMP@PAM hydrogel showed a balanced photothermal effect, mechanical property, and osteogenesis for MDA-NPs can be used as a co-crosslinker, photothermal agent, and Mg2+ reservoir. Human OS cells (143B) could be efficiently inhibited by 5NP/CMP@PAM hydrogel with near-infrared (NIR) laser irradiation, achieving complete suppression of tumor recurrence in vitro and in vivo. The released Mg2+ efficiently promotes the osteogenic activities of mouse embryo osteoblast precursor cells (MC3T3-E1) and 5NP/CMP@PAM hydrogels exhibit highly effective bone repair performance in a critical cranial defect rat model. In conclusion, the 5NP/CMP@PAM hydrogel demonstrated excellent dual functions of suppressing OS recurrence and repairing bone defects. This novel multifunctional bioactive hydrogel provides an encouraging idea of synergistic postoperative treatment of OS.

Supramolecular semiquinone radicals confined with DNAzymes for dissipative ROS generation and therapy

Current reactive oxygen species (ROS)-regulating materials for disease treatments are always at turn-on state, leading to long-lasting inflammation and chronic wound healing. Inspired by the process of Coenzyme Q (CoQ)-mediated ROS formation in the mitochondrial electron transport chain (ETC), a dissipative ROS nanogenerator possessing energy storage function and horseradish peroxidase (HRP)-mimicking activity was realized by a type of ternary composite nanosheets. Specifically, semiquinone radicals generated from polydopamine polymerization were captured and stabilized by supramolecular DNA scaffolds hosts, i.e. G-quadruplexes/hemin (GH) complexes with large π-planes of bases and interplane spaces. As a consequence, semiquinone radicals served as electron donor to oxygen for generating H2O2 which could be utilized by the neighboring GH to generate hydroxyl radicals (•OH) at weakly acidic conditions. The cascade catalytic activity remained above 93% and 45% after 20, 60 days of storage in N2 saturated solution. However, it was consumptively attenuated (~22 h of dissipation duration) due to the electron depletion/exhaustion of semiquinone radicals at pathological conditions. Thereby, effective inhibition of tumor recurrence and wound infection, as well as accelerated tissue repair were achieved in tumor postoperative treatments. This system significantly advances ROS regulators for integrative therapy.

Transient increase in recurrent inhibition in amyotrophic lateral sclerosis as a putative protection from neurodegeneration.

Adaptive mechanisms in spinal circuits are likely involved in homeostatic responses to maintain motor output in amyotrophic lateral sclerosis. Given the role of Renshaw cells in regulating the motoneuron input/output gain, we investigated the modulation of heteronymous recurrent inhibition. Electrical stimulations were used to activate recurrent collaterals resulting in the Hoffmann reflex depression. Inhibitions from soleus motor axons to quadriceps motoneurons, and vice versa, were tested in 38 patients and matched group of 42 controls. Compared with controls, the mean depression of quadriceps reflex was larger in patients, while that of soleus was smaller, suggesting that heteronymous recurrent inhibition was enhanced in quadriceps but reduced in soleus. The modulation of recurrent inhibition was linked to the size of maximal direct motor response and lower limb dysfunctions, suggesting a significant relationship with the integrity of the target motoneuron pool and functional abilities. No significant link was found between the integrity of motor axons activating Renshaw cells and the level of inhibition. Enhanced inhibition was particularly observed in patients within the first year after symptom onset and with slow progression of lower limb dysfunctions. Normal or reduced inhibitions were mainly observed in patients with motor weakness first in lower limbs and greater dysfunctions in lower limbs. We provide the first evidence for enhanced recurrent inhibition and speculate that Renshaw cells might have transient protective role on motoneuron by counteracting hyperexcitability at early stages. Several mechanisms likely participate including cortical influence on Renshaw cell and reinnervation by slow motoneurons.

Local feedback inhibition tightly controls rapid formation of hippocampal place fields

Hippocampal place cells underlie spatial navigation and memory. Remarkably, CA1 pyramidal neurons can form new place fields within a single trial by undergoing rapid plasticity. However, local feedback circuits likely restrict the rapid recruitment of individual neurons into ensemble representations. This interaction between circuit dynamics and rapid feature coding remains unexplored. Here, we developed "all-optical" approaches combining novel optogenetic induction of rapidly forming place fields with 2-photon activity imaging during spatial navigation in mice. We find that induction efficacy depends strongly on the density of co-activated neurons. Place fields can be reliably induced in single cells, but induction fails during co-activation of larger subpopulations due to local circuit constraints imposed by recurrent inhibition. Temporary relief of local inhibition permits the simultaneous induction of place fields in larger ensembles. We demonstrate the behavioral implications of these dynamics, showing that our ensemble place field induction protocol can enhance subsequent spatial association learning.

Inhibition of tumor recurrence and metastasis via a surgical tumor-derived personalized hydrogel vaccine.

Tumor recurrence and metastasis have become thorny problems in clinical tumor therapy. Vaccine-mediated antitumor immune response has emerged as a significant postoperative inhibition for tumor recurrence and metastasis. However, limited tumor antigens are not conducive to trigger complete antigen-specific T cell-mediated immune responses. Herein, the design of a hydrogel vaccine system containing a granulocyte-macrophage colony stimulating factor (GM-CSF), based on surgically removed tumor cell lysates, was reported. The hydrogel was formed by crosslinking tumor cell lysates and alginate at low temperatures. The GM-CSF was released from the hydrogel to recruit dendritic cells (DCs), which provided a completely personalized tumor antigen pool. They were combined to foster the production of powerful antigen-specific T cells. The personalized hydrogel was implanted at the surgical site and it stimulated the antitumor immune response for the inhibition of residual tumor cells. Delightfully, the personalized hydrogel inhibited the tumor recurrence and metastasis well in a post-surgical mice tumor model, in combination with a programmed death-ligand 1 antibody (αPD-L1). The results demonstrated that the development of a personalized hydrogel and a combination of αPD-L1 provided a new strategy to prevent tumor recurrence and metastasis.

Biodegradable electrospun nanofibrous platform integrating antiplatelet therapy-chemotherapy for preventing postoperative tumor recurrence and metastasis

The perioperative trauma-related platelet recruitment and activation severely affect tumor recurrence and metastasis. Therefore, efficiently killing residual tumor cells and simultaneously inhibiting platelet activation to block platelet-cancer cell interaction might be a promising strategy to prevent postoperative tumor recurrence and metastasis.Methods: Biodegradable PLGA electrospun nanofibrous films co-delivering doxorubicin-loaded tumor repopulating cell-derived microparticles (DOX-MPs) and aspirin (ASA) were developed as the implant materials (DOX-MPs/ASA@NF) for postoperative in-situ treatment. The characterization, cytotoxicity against tumor cells, inhibition in platelet activation-triggered proliferation, migration and metastasis of tumor cells and in vivo anti-recurrence and anti-metastasis activity induced by DOX-MPs/ASA@NF were systematically evaluated.Results: PLGA nanofibrous films facilitate the enhanced distribution of DOX-MPs as well as DOX-MPs and ASA release in a time-programmed manner within the tumor resection cavity. The released DOX-MPs efficiently kill the residual tumor cells, while ASA decreases platelet activation and inhibits platelet-promoted proliferation, migration and metastasis of tumor cells, resulting in the remarkable inhibition of postoperative tumor recurrence and metastasis.Conclusions: DOX-MPs/ASA@NF may be a promising candidate to prevent the recurrence and metastasis of resectable tumors.

Kv3 Channels Contribute to the Excitability of Subpopulations of Spinal Cord Neurons in Lamina VII.

Autonomic parasympathetic preganglionic neurons (PGNs) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be because of recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within Lamina VII, where PGN are situated, by combining whole cell patch clamp recordings with k-means clustering of a range of electrophysiological parameters. Additional morphologic analysis separated these neuronal classes into parasympathetic preganglionic populations (PGN) and a fast-firing interneuronal population. Kv3 channels are voltage-gated potassium channels (Kv) that allow fast and precise firing of neurons. We found that blockade of Kv3 channels by tetraethylammonium (TEA) reduced neuronal firing frequency and isolated high-voltage-activated Kv currents in the fast-firing population but had no effect in PGN populations. Furthermore, Kv3 blockade potentiated the local and descending inhibitory inputs to PGN indicating that Kv3-expressing inhibitory neurons are synaptically connected to PGN. Taken together, our data reveal that Kv3 channels are crucial for fast and regulated neuronal output of a defined population that may be involved in intrinsic spinal bladder circuits that underpin recurrent inhibition of PGN.

Polydopamine-Doped Supramolecular Chiral Hydrogels for Postoperative Tumor Recurrence Inhibition and Simultaneously Enhanced Wound Repair

Polydopamine-Doped Supramolecular Chiral Hydrogels for Postoperative Tumor Recurrence Inhibition and Simultaneously Enhanced Wound Repair

Local delivery of biocompatible lentinan/chitosan composite for prolonged inhibition of postoperative breast cancer recurrence

Postsurgical localized chemotherapy for breast cancer recurrence (BCR) still faces many problems which dampen researchers' enthusiasm and discounted prognosis. Simple strategies with controllable toxicities are expected to address these hurdles. Lentinan (LNT) has excellent biocompatibility and notable antitumor activity but rather low bioavailability after intravenous or oral administration. Here, a sponge-like LNT/chitosan composite (LNT/CS sponge) was prepared for efficient local delivery to prevent postoperative BCR. The obtained sponges exhibit uniform porosity and sustained release of LNT in vitro and in vivo. Furthermore, the sponges were implanted and showed significant reduction of postsurgical recurrence and suppression of long-term tumor regrowth with favorable biocompatibility in a subcutaneous postsurgical recurrence mouse model. Subsequent studies revealed that LNT can restrain the stemness of breast cancer cells, which may account for the long-term inhibition of tumor relapse. Therefore, LNT/CS sponge has a great potential as a promising alternative for postsurgical BCR.

Engineered Iron-Based nanoplatform amplifies repolarization of M2-Like Tumor-Associated Macrophages for enhanced cancer immunotherapy

Resetting M2-like tumor-associated macrophages (TAMs) to antitumor M1 phenotype is a promising strategy in cancer immunotherapy. Although iron-based nanoparticles exhibit the potential of M2-to-M1 macrophage repolarization, the efficient M2-like TAM targeting and the subsequent intracellular iron retention remains a big challenge. Here, M2 macrophage-targeting peptide-conjugated iron-based metal–organic frameworks are developed to load diclofenac (Dic@M2pep-Fe-MOF) for enhanced cancer immunotherapy. Dic@M2pep-Fe-MOF efficiently targets M2-like TAMs and decreases the efflux by hepcidin/ferroportin signaling pathway, enabling enhanced intracellular accumulation for improved M2-to-M1 macrophage repolarization. Dic@M2pep-Fe-MOF-repolarized M2-like TAMs efficiently kill and phagocytose tumor cells, and importantly remodel tumor immune microenvironment to generate long-term antitumor immune memory, eliciting strong anticancer efficacy with tumor recurrence inhibition. Our results support Dic@M2pep-Fe-MOF as a potential drug for cancer immunotherapy.

Multifunctional Flavonoid-Silica Nanohydrogel Enables Simultaneous Inhibition of Tumor Recurrence and Bacterial Infection in Post-Surgical Treatment.

A strategy to synthesize water-soluble and fluorescent flavonoid-silica nanocomposites (FSiNCs) simultaneously featuring anti-tumor and anti-bacterial abilities is developed. Furthermore, it is demonstrated that the therapeutic effects of FSiNCs are associated with the selective accumulation of reactive oxide species in both tumor and bacteria cells. Following that, the resultant FSiNCs are incorporated with thrombin and fibrinogen, being sprayed onto the tumor surgical wound site to in situ form fibrin gel (FSiNCs@Fibrin). Remarkably, such FSiNCs@Fibrin results in an ≈18-fold reduction in intratumoral bacteria numbers and ≈12-fold decrease in tumor regrowth compared to equivalent free flavonoid-loaded gel.

Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment.

Despite multiple immunotherapeutic technologies that achieve potent T cell activation, effector T cells still lack efficiency because of the highly immunosuppressive conditions in the tumor microenvironment. Inspired by recent advances in nano-sized secreted vesicles known as exosomes as therapeutic agents and research revealing that circulating cancer cells have a “homing” capacity to return to the main tumor sites, we generated macrophage-tumor hybrid cells. We introduced nuclei isolated from tumor cells into activated M1-like macrophages to produce chimeric exosomes (aMT-exos). The aMT-exos were able to accumulate in both lymph nodes and diverse tumors of xenograft mice. They entered lymph nodes and primed T cell activation in both the classical antigen-presenting cell–induced immunostimulatory manner and a unique “direct exosome interaction” manner. aMT-exos also had strong “homing behavior” to tumor sites, where they ameliorated immunosuppression. They were effective in inducing tumor regression and extending survival in primary mouse models of lymphoma and breast and melanoma cancers. In addition, when combined with anti–programmed death 1 (a-PD1) treatment, aMT-exos were able to extend survival of metastatic and postsurgical tumor recurrence mouse models. Such a coactivation of the immune response and the tumor microenvironment enabled aMT-exos to confer efficient inhibition of primary tumors, tumor metastases, and postoperative tumor recurrence for personalized immunotherapy, which warrants further exploration in the clinical setting.

Multifunctional Magnesium Anastomosis Staples for Wound Closure and Inhibition of Tumor Recurrence and Metastasis.

Biodegradable magnesium (Mg) implants spontaneously releasing therapeutic agents against tumors are an intriguing therapeutic approach for both tissue repair and tumor treatment. Anastomotic staples are extensively used for wound closure after surgical resection in patients with colorectal tumors. However, the safety of Mg anastomosis implants for intestinal closure and the effect of tumor suppression remain elusive. Here, we used a high-purity Mg staple to study these issues. Based on the results, we found that it has the potential to heal wounds produced after colorectal tumor resection while inhibiting relapse of residual tumor cells in vitro and in vivo. After implantation of Mg staples for 7 weeks in rabbits, the intestinal wound gradually healed with no adverse effects such as leakage or inflammation. Furthermore, the implanted Mg staples inhibit the growth of colorectal tumor cells and block migration to normal organs because of the increased concentration of Mg ions and released hydrogen. Such an antitumor effect is further confirmed by the in vitro cell experiments. Mg significantly induces apoptosis of tumor cells as well as inhibits cell growth and migration. Our work presents a feasible therapeutic opinion to design Mg anastomotic staples to perform wound healing and simultaneously release tumor suppressor elements in vivo to decrease the risk of tumor recurrence and metastasis.