Efficient Tumor Therapy Research Articles

Bioactive Metal-Organic Frameworks with Specific Metal-Nitrogen (M-N) Active Sites for Efficient Sonodynamic Tumor Therapy.

Sonodynamic therapy (SDT) offers an efficient noninvasive strategy for cancer treatment. However, the efficiency of SDT is limited by the structural and physicochemical properties of ultrasound (US)-sensitive agents. Here, we discover the combination of bioactivity and sonodynamic properties of zeolite imidazolium framework-8 nanocrystals (ZIF-8 NCs) for efficient tumor therapy. ZIF-8 NCs are susceptible to biodegradation to release zinc ions (Zn2+) triggered by the weakly acidic tumor microenvironment, demonstrating the bioactivity to induce apoptosis in cancer cells. Density functional theory calculations combined with experiments revealed that the unsaturated zinc-nitrogen (Zn-N) active sites on the surface of ZIF-8 NCs allow an enhanced electron transfer via ligand to metal charge transfer bands from the highest occupied molecular orbitals to the lowest unoccupied molecular orbitals. This process is critical for the generation of reactive oxygen species by metal-organic frameworks (MOFs) under US irradiation. In vivo experiments show that ZIF-8 NCs exhibit high tumor inhibition efficiency (84.6%) as both a bioactive anticancer agent and a sonosensitizer. We believe that this study can expand the application of MOFs and contribute to a better understanding of the mechanism of action of sonosensitizers.

Novel Fluorinated Spermine and Small Molecule PEI to Deliver Anti-PD-L1 and Anti-VEGF siRNA for Highly Efficient Tumor Therapy.

Small interfering RNA (siRNA) can specifically silence disease gene expression. This project investigated the overexpression of programmed death receptor ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) on the surface of tumor cells. However, the main obstacle to the development of gene therapy drugs is the lack of an efficient delivery vector, which should be able to overcome multiple delivery barriers and protect siRNA to enter the target cells. Therefore, a novel fluorine-modified endogenous molecular carrier TFSPEI was constructed by linking fluorinated groups with hydrophobic and hydrophilic characteristics on the surface of PEI and spermine. The results showed that lower toxicity, higher endocytosis, and silencing efficiency were achieved. We found that the inhibition of VEGF targets can indirectly activate the immune response to promote the tumor-killing and invasion effects of T cells. The combined delivery of anti-VEGF siRNA and anti-PD-L1 siRNA could inhibit the expression of corresponding proteins, restore the anti-tumor function of T cells and inhibit the growth of neovascularization, and obtained significant anti-tumor effects. Therefore, this safe and efficient fluorinated spermine and small molecule PEI-based anti-PD-L1 and anti-VEGF siRNA delivery system is expected to provide a new strategy for gene therapy of tumors.

Precise Regulation of Enzyme-Nanozyme Cascade Reaction Kinetics by Magnetic Actuation toward Efficient Tumor Therapy.

Spatiotemporal regulation of multi-enzyme catalysis with stimuli is crucial in nature to meet different metabolic requirements but presents a challenge in artificial cascade systems. Here, we report a strategy for precise and tunable modulation of enzyme-nanozyme cascade reaction kinetics by remote magnetic stimulation. As a proof of concept, glucose oxidase (GOx) was immobilized onto a ferrimagnetic vortex iron oxide nanoring (Fe3O4 NR) functionalized with poly(ethylene glycol) of different molecular weights to construct a series of Fe3O4 NR@GOx with nanometer linking distances. The activities of GOx and the Fe3O4 NR nanozyme in these systems were shown to be differentially stimulated by Fe3O4 NR-mediated local heat in response to an alternating magnetic field (AMF), leading to modulated cascade reaction kinetics in a distance-dependent manner. Compared to the free GOx and Fe3O4 NR mixture, Fe3O4 NR(D2)@GOx with an optimum linking distance of 1 nm exhibits a superior kinetic match between GOx and the Fe3O4 NR nanozyme and over a 400-fold higher cascade activity under AMF exposure. This enables remarkable intracellular reactive oxygen species production and significantly improved tumor inhibition of AMF-stimulated Fe3O4 NR(D2)@GOx in 4T1 tumor-bearing mice. The strategy reported here offers a straightforward new tool for fine-tuning multi-enzyme catalysis at the molecular level using magnetic stimuli and holds great promise for use in a variety of biotechnology and synthetic biology applications.

Redox Control of the Dormant Cancer Cell Life Cycle.

Following efficient tumor therapy, some cancer cells may survive through a dormancy process, contributing to tumor recurrence and worse outcomes. Dormancy is considered a process where most cancer cells in a tumor cell population are quiescent with no, or only slow, proliferation. Recent advances indicate that redox mechanisms control the dormant cancer cell life cycle, including dormancy entrance, long-term dormancy, and metastatic relapse. This regulatory network is orchestrated mainly through redox modification on key regulators or global change of reactive oxygen species (ROS) levels in dormant cancer cells. Encouragingly, several strategies targeting redox signaling, including sleeping, awaking, or killing dormant cancer cells are currently under early clinical evaluation. However, the molecular mechanisms underlying redox control of the dormant cancer cell cycle are poorly understood and need further exploration. In this review, we discuss the underlying molecular basis of redox signaling in the cell life cycle of dormant cancer and the potential redox-based targeting strategies for eliminating dormant cancer cells.

A diketopyrrolopyrrole-based conjugated polymer for efficient photodynamic and photothermal combination therapy under single 808 nm laser irradiation

Photodynamic therapy (PDT) and photothermal therapy (PTT) are two powerful tools to tackle cancer in the biomedical field due to their super tumor ablation efficiency and minimal damage to normal tissue. However, it is still a tricky challenge to combine these two treatment modalities into a single agent for single wavelength laser triggered efficient tumor therapy. Herein, water-soluble nanoparticles consisting of diketopyrrolopyrrole-based conjugated polymer and amphipathic Pluronic F127 were intelligently devised and fabricated, which possessed outstanding optical properties, superb biocompatibility, excellent photostability. Surprisingly, the nanoparticles exhibited moderate singlet oxygen yield (2.34%) and photothermal conversion efficiency (41.5%) under an 808 nm laser illumination, which was in favor of achieving high-performance PDT/PTT combination therapy. Moreover, the evident antitumor effect of the nanoparticles was confirmed by in vitro and in vivo experiments. This work provides a promising approach to rationally design near infrared absorbing organic polymer nanoplatforms for combination cancer therapy.

Nanoengineered biomimetic Cu-based nanoparticles for multifunational and efficient tumor treatment

The microwave dynamic therapy (MDT) mediated by cytotoxic reactive oxygen species (ROS) is a promising anticancer therapeutic method. However, the therapeutic efficiency of MDT is restricted by several limitations including insufficient ROS generation, strong proangiogenic response, and low tumor-targeting efficiency. Herein, we find that Cu-based nanoparticles can produce oxygen under microwave (MW) irradiation to raise the generation of ROS, such as •O2, •OH and 1O2, especially •O2. On this basis, a nanoengineered biomimetic strategy is designed to improve the efficiency of MDT. After intravenous administration, the nanoparticles accumulate to the tumor site through targeting effect mediated by biomimetic modification, and it can continuously produce oxygen to raise the levels of ROS in tumor microenvironment under MW irradiation for MDT. Additionally, Apatinib is incorporated as antiangiogenic drug to downregulate the expression of vascular endothelial growth factor (VEGF), which can effectively inhibit the tumor angiogenesis after MDT. Hence, the tumor inhibition rate is as high as 96.79%. This study provides emerging strategies to develop multifunctional nanosystems for efficient tumor therapy by MDT.

Ultrasmall Barium Titanate Nanoparticles for Highly Efficient Hypoxic Tumor Therapy via Ultrasound Triggered Piezocatalysis and Water Splitting.

Hypoxia in a solid tumor microenvironment (TME) can lead to the overexpression of hypoxia-inducible factor-1α (HIF-1α), which correlates to tumor metastasis. Reactive oxygen species (ROS) induced tumor cell apoptosis is becoming a promising method in tumor treatment. Currently, the ROS generating systems, e.g., photodynamic treatment and sonodynamic treatment, highly depend on oxygen (O2) in the tumor microenvironment (TME). However, the level of O2 in TME is too low to produce enough ROS. Herein, we developed an ultrasmall DSPE-PEG2000 coated barium titanate nanoparticle (P-BTO) for tumor treatment based on ultrasound triggered piezocatalysis and water splitting. Interestingly, irradiated by ultrasound, the surface of ultasmall P-BTO nanoparticles produced imbalance charges, which induced a cascade of redox reaction processes to simultaneously generate ROS and O2, the latter one was hardly generated in large-sized barium titanate nanoparticles. The as-synthesized P-BTO reached the highest accumulation in the tumor site at 4 h after intravenous injection. The results showed that the produced O2 significantly alleviated the hypoxia of TME to down-regulate the expression of HIF-1α, and the produced ROS can efficiently kill tumor cells. Moreover, the tumor metastasis was also inhibited, providing a different way to treat triple-negative breast cancer, which was easily metastatic and lacked effective treatments in the clinic.

GSH‐Depleted Nanozymes with Dual‐Radicals Enzyme Activities for Tumor Synergic Therapy

AbstractAlthough inspiring progress has been achieved in tumor nanocatalytic therapies based on tailor‐made nanozymes for converting hydrogen peroxide into reactive oxygen species (ROS) efficiently, most cytotoxic hydroxyl radicals do not spread far enough within a cell to damage the primary organelles for effective tumor therapy due to their short half‐life time (≈1 µs). Developing a novel nanocatalyst platform involving longer half‐life time ROS is desired. To this end, Fe3O4‐Schwertmannite nanocomposites (Fe3O4‐Sch) with triple‐effect tumor therapy are constructed through a facile method. The Schwertmannite shell converts the •OH produced by Fe3O4 via the Fenton reaction into sulfate radicals with a longer half‐life time (30 µs). Combination of dual radicals exhibits overwhelming tumor inhibition efficacy. The nanocomposites also show the multifunctionality of good photothermal efficiency (33.2%) and synergistic oxidative stress amplification upon glutathione biosynthesis (GSH) depletion by the l‐buthionine sulfoximine (BSO) molecules loaded in the hollow Fe3O4 cores. The comprehensive properties of the nanoplatform including the dual‐radical production, Fe3O4 nanocrystal mediated PTT, and the BSO mediated GSH depletion result in remarkable tumor inhibition both in vitro and in vivo, which may pave a way to constructing a synergic catalytic nanoplatform for efficient tumor therapy.

Multifunctional Protein-Decorated Bioactive Glass Nanoparticles for Tumor-Specific Therapy and Bioimaging In Vitro and In Vivo.

Multifunctional nanocarriers with a simple structure and biocompatibility for bioimaging, potential tumor targeting, and precise antitumor ability are promising in cancer therapy. Bioactive glass is an important biomaterial and has been used in clinical bone tissue repair due to the high biocompatibility and bioactivity. Herein, we report fetal bovine serum (FBS)-decorated europium-doped bioactive glass nanoparticles (EuBGN@FBS) with excellent biosafety and enhanced tumor targeting for cancer imaging and therapy. EuBGN@FBS showed the controlled photoluminescent properties and pH-responsive anticancer drug release behavior. The FBS decoration significantly enhanced the dispersibility in physiological medium and improved hemocompatibility and cellular uptake of EuBGN. Relative to EuBGN, EuBGN@FBS could also efficiently image the cancer cell and show significantly enhanced targeted tumor imaging and chemotherapy in vivo while retaining negligible side effects. The simple and biocompatible structure with efficient tumor targeting, imaging, and therapy makes EuBGN@FBS highly promising in future cancer therapy.

Near-Infrared Photo-controlled Permeability of a Biomimetic Polymersome with Sustained Drug Release and Efficient Tumor Therapy.

Synthetic polymersomes have structure similarity to bio-vesicles and could disassemble in response to stimuli for "on-demand" release of encapsulated cargos. Though widely applied as a drug delivery carrier, the burst release mode with structure complete destruction is usually taken for most responsive polymersomes, which would shorten the effective drug reaction time and impair the therapeutic effect. Inspired by the cell organelles' communication mode via regulating membrane permeability for transportation control, we highlight here a biomimetic polymersome with sustained drug release over a specific period of time via near-infrared (NIR) pre-activation. The polymersome is prepared by the self-assembling amphiphilic diblock copolymer P(OEGMA-co-EoS)-b-PNBOC and encapsulates the hypoxia-activated prodrug AQ4N and upconversion nanoparticle (PEG-UCNP) in its hydrophilic centric cavity. Thirty minutes of NIR pre-activation triggers cross-linking of NBOC and converts the permeability of the polymersome with sustained AQ4N release until 24 h after the NIR pre-activation. The photosensitizer EoS is activated and aggravates environmental hypoxic conditions during a sustained drug release period to boost the AQ4N therapeutic effect. The combination of sustained drug release with concurrent hypoxia intensification results in a highly efficient tumor therapeutic effect both intracellularly and in vivo. This biomimetic polymersome will provide an effective and universal tumor therapeutic approach.

Stimuli‐Responsive Nanotheranostics

Stimuli‐Responsive Nanotheranostics

Single injection and multiple treatments: An injectable nanozyme hydrogel as AIEgen reservoir and release controller for efficient tumor therapy

• AIEgens loaded thermo-sensitive hydrogel was used to achieve the goal of multiple intratumoral treatment with one injection. • Prussian blue nanoparticles were used to improve the hypoxic microenvironment of tumor. • Prussian blue nanoparticles enhance the therapeutic effect of AIEgen based PDT. Scheme 1. Schematic illustration of an injectable nanozyme hydrogel as AIEgen release controller for efficient tumor therapy. Direct intratumoral injection of aggregation-induced emission luminogen (AIEgen) enable direct photodynamic therapy (PDT) of tumors, but these injections may cause localized pain and a range of postoperative complications during frequent injections. In the present study, we developed a novel injectable nanozyme hydrogel that functions as AIEgens reservoir and release controller (ARC) and thereby facilitates more efficient tumor therapy. The ARC system was developed by simultaneously encapsulating Prussian blue (PB) nanoparticles and an AIEgen (CQu) in agarose hydrogels. PB converts near-infrared laser into heat, resulting in agarose degradation and consequent CQu release. Then PB nanozyme can drive the decomposition of endogenous hydrogen peroxide, then yielding oxygen (O 2 ) generation. Following subsequent low-power white light exposure, AIEgens can generate high levels of reactive oxygen species (ROS) with sufficient O 2 , thereby inducing tumor cell cytotoxicity. As hydrogels can persist within tumors for a minimum of 48 h, they can facilitate multiple rounds of treatment following a single injection. The present study is the first attempt to utilize hydrogel for AIEgens delivery, and the ARC system developed herein offers a novel means of supporting the clinical development of AIEgens treatment strategies for cancer patients.

Tumor Microenvironment Sensitive Nanocarriers for Bioimaging and Therapeutics.

The tumor microenvironment (TME), which is composed of cancer cells, stromal cells, immune cells, and extracellular matrices, plays an important role in tumor growth and progression. Thus, targeting the TME using a well-designed nano-drug delivery system is emerging as a promising strategy for the treatment of solid tumors. Compared to normal tissues, the TME presents several distinguishable physiological features such as mildly acidic pH, hypoxia, high level of reactive oxygen species, and overexpression of specific enzymes, that are exploited as stimuli to induce specific changes in the nanocarrier structures, and thereby facilitates target-specific delivery of imaging or chemotherapeutic agents for the early diagnosis or effective treatment, respectively. Recently, smart nanocarriers that respond to more than one stimulus in the TME have also been designed to elicit a more desirable spatiotemporally controlled drug release. This review highlights the recent progress in TME-sensitive nanocarriers designed for more efficient tumor therapy and imaging. In particular, the design strategies, challenges, and critical considerations involved in the fabrication of TME-sensitive nanocarriers, along with their in vitro and in vivo evaluations are discussed.

Combination of tumor fragments and nanotechnology as a therapeutic approach: Treating a tumor with tumor

Cancer with high mortality is a serious threat to human health. Thus, favorable approaches for efficient elimination of tumors are urgently needed. Recently, a new antitumor strategy of tumor-derived fragments (TDFs) interfered with nanotechnology has been developed for highly specific and efficient tumor therapy. On one hand, TDF-based nanoformulations (termed as TDF-NFs) and nanoparticle-induced immunogenic dying tumor cells (IDTCs) can act as ex situ/in situ vaccines to elicit the immune responses for cancer immunotherapy. On the other hand, TDF-NFs can be drug carriers for cancer theranostics. In this review, the immune regulation mechanisms of various TDFs including tumor-derived DNA/RNA, tumor cell membranes, tumor-derived exosomes, whole tumor lysates, and IDTCs are summarized, and the applications of nanotechnology-intervened TDFs as vaccines and vehicles in tumor therapy are also highlighted. It is hoped that the review will inspire researchers to further construct functional TDF-based nanovaccines and nanocarriers, facilitating the development of novel antitumor strategies.

Hypoxia-stimulated tumor therapy associated with the inhibition of cancer cell stemness

Cancer stem cells (CSCs) possess self-renewal and clonal tumor initiation capacities, which lead to drug resistance and tumor recurrence. In this work, a hypoxia-stimulated strategy based on a smart triblock vector was developed to enhance therapeutic efficacy through the inhibition of cancer stemness. The triblock precursor was designed with a fluorescence chromophore for monitoring hypoxia, a methoxy nitro-unit for biorecognition, and a poly(ethylene glycol)-folate for cancer cell targeting. As the degree of hypoxia increases, the vectors were progressively dissociated as indicated by the enhanced fluorescence intensity in hypoxic cells and compacted three-dimensional spheres. Furthermore, the expression of stem cell markers such as CD133 and SOX2 was significantly inhibited, and the serial passaging of CSCs was notably impaired after treating CSCs with the vectors. The inhibition of cancer cell stemness significantly improved the anticancer efficiency in vivo. Moreover, tumor initiation was reduced and the median survival time of xenograft tumor models was prolonged by regulating cell stemness under hypoxia. Overall, this work provides a promising approach to inhibit tumor resistance and recurrence for efficient tumor therapy.

Injectable biodegradation-visual self-healing citrate hydrogel with high tissue penetration for microenvironment-responsive degradation and local tumor therapy

Local tumor therapy through injectable biodegradable hydrogels with controlled drug release has attracted much attention recently, due to their easy operation, low side effect and efficiency. However, most of the reported therapeutic hydrogel system showed a lack of biodegradation tracking and tumor environment-responsive degradation/therapy. Herein, we developed a multifunctional injectable biodegradation-visual citric acid-based self-healing scaffolds with microenvironment-responsive degradation and drug release for safe and efficient skin tumor therapy (FPRC hydrogel). FPRC scaffolds possess multifunctional properties including thermosensitive, injectable, self-healing, photoluminescent and pH-responsive degradation/drug release. The FPRC scaffolds with strong red fluorescence which has good photostability, tissue penetration and biocompatibility can be tracked and monitored to evaluate the degradation of the scaffolds in vivo. Moreover, the FPRC scaffolds showed pH-responsive doxorubicin (DOX) release, efficiently killed the A375 cancer cell in vitro and suppressed the tumor growth in vivo. Compared to the free drug (DOX), the FPRC@DOX scaffolds displayed a significantly high therapeutic effect and less biotoxicity. This work provides an alternative strategy to design smart visual scaffolds for tumor therapy and regenerative medicine.

Biomimetic CoO@AuPt nanozyme responsive to multiple tumor microenvironmental clues for augmenting chemodynamic therapy

Chemodynamic therapy (CDT), an emerging therapeutic strategy, has been recently exploited for in situ treatment through Fenton or Fenton-like reactions to generate cytotoxic reactive oxygen species (ROS). However, current systems rely significantly on the high local oxygen levels and strongly acidic conditions (pH = 3.0–5.0). Simultaneously, the produced ROS can be rapidly consumed by intracellular glutathione (GSH) in the electron transport chain. Herein, an original and biomimetic CoO@AuPt nanocatalyst was prepared based on the assembly of Au and Pt nanoparticles (NPs) on the surface of hollow CoO nanocapsules. The as-synthesized nanozyme exhibits extremely high stability under physiological conditions, whereas it undergoes spontaneous disintegration in the unique tumor microenvironment (TME). Subsequently, the decomposition products can catalyze a cascade of biochemical reactions to produce abundant ROS without any external stimuli. Thus, the present nanoplatform can increase intracellular ROS levels through continuous supply of H2O2, relief of local hypoxia and depletion of GSH, which result in remarkable and specific tumor damage both in vitro and in vivo. The findings of this study highlight the promising potential of CoO@AuPt nanocatalyst as a TME-responsive CDT nanomagnet for highly efficient tumor therapy.

Biodegradable pH-responsive micelles loaded with 8-hydroxyquinoline glycoconjugates for Warburg effect based tumor targeting

Biodegradable triblock copolymer poly(ethylene glycol)-b-polycarbonate-b-oligo([R]-3-hydroxybutyrate) was prepared via metal-free ring-opening polymerization of ketal protected six-membered cyclic carbonate followed by esterification with bacterial oligo([R]-3-hydroxybutyrate) (oPHB). Amphiphilic triblock copolymer self-organizes into micelles with a diameter of ~25 nm. Acid-triggered hydrolysis of ketal groups to two hydroxyl groups causes an increase in hydrophilicity of the hydrophobic micelle core, resulting in the micelles swell and drug release. oPHB was added as core-forming block to increase the stability of prepared micelles in all pH (7.4, 6.4, 5.5) studied. Doxorubicin and 8-hydroxyquinoline glucose- and galactose conjugates were loaded in the micelles. In vitro drug release profiles in PBS buffers with different pH showed that a small amount of loaded drug was released in PBS at pH 7.4, while the drug was released much faster at pH 5.5. MTT assay showed that the blank micelles were non-toxic to different cell lines, while glycoconjugates-loaded micelles, showed significantly increased ability to inhibit the proliferation of MCF-7 and HCT-116 cells compared to free glycoconjugates. The glycoconjugation of anti-cancer drugs and pH-responsive nanocarriers have separately shown great potential to increase the tumor-targeted drug delivery efficiency. The combination of drug glycoconjugation and the use of pH-responsive nanocarrier opens up new possibilities to develop novel strategies for efficient tumor therapy.

NIR-II driven plasmon-enhanced cascade reaction for tumor microenvironment-regulated catalytic therapy based on bio-breakable Au–Ag nanozyme

Emerging nanozymes with natural enzyme-mimicking catalytic activities have inspired extensive research interests due to their high stability, low cost, and simple preparation, especially in the field of catalytic tumor therapy. Here, bio-breakable nanozymes based on glucose-oxidase (GOx)-loaded biomimetic Au–Ag hollow nanotriangles (Au–Ag–GOx HTNs) are designed, and they trigger an near-infrared (NIR)-II-driven plasmon-enhanced cascade catalytic reaction through regulating tumor microenvironment (TME) for highly efficient tumor therapy. Firstly, GOx can effectively trigger the generation of gluconic acid (H+) and hydrogen peroxide (H2O2), thus depleting nutrients in the tumor cells as well as modifying TME to provide conditions for subsequent peroxidase (POD)-like activity. Secondly, NIR-II induced surface plasmon resonance can induce hot electrons to enhance the catalytic activity of Au–Ag–GOx HTNs, eventually boosting the generation of hydroxyl radicals (•OH). Interestingly, the generated H2O2 and H+ can simultaneously induce the degradation of Ag nanoprisms to break the intact triangle nanostructure, thus promoting the excretion of Au–Ag–GOx HTNs to avoid the potential risks of drug metabolism. Overall, the NIR-II driven plasmon-enhanced catalytic mechanism of this bio-breakable nanozyme provides a promising approach for the development of nanozymes in tumor therapy.

Engineering 2D Mesoporous Silica@MXene-Integrated 3D-Printing Scaffolds for Combinatory Osteosarcoma Therapy and NO-Augmented Bone Regeneration.

The rising concerns of the recurrence and bone deficiency in surgical treatment of malignant bone tumors have raised an urgent need of the advance of multifunctional therapeutic platforms for efficient tumor therapy and bone regeneration. Herein, the construction of a multifunctional biomaterial system is reported by the integration of 2D Nb2 C MXene wrapped with S-nitrosothiol (RSNO)-grafted mesoporous silica with 3D-printing bioactive glass (BG) scaffolds (MBS). The near infrared (NIR)-triggered photonic hyperthermia of MXene in the NIR-II biowindow and precisely controlled nitric oxide (NO) release are coordinated for multitarget ablation of bone tumors to enhance localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from BG scaffold promote bone-regeneration bioactivity, augmented by sufficient blood supply triggered by on-demand NO release. The tunable NO generation plays a crucial role in sequential adjuvant tumor ablation, combinatory promotion of coupled vascularization, and bone regeneration. This study demonstrates a combinatory osteosarcoma ablation and a full osseous regeneration as enabled by the implantation of MBS. The design of multifunctional scaffolds with the specific features of controllable NO release, highly efficient photothermal conversion, and stimulatory bone regeneration provides an intriguing biomaterial platform for the diversified treatment of bone tumors.