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Immunotherapy harnesses the inherent immune system in the body to generate systemic antitumor immunity, offering a promising modality for defending against cancer. However, tumor immunosuppression and evasion seriously restrict the immune response rates in clinical settings. Catalytic nanomedicines can transform tumoral substances/metabolites into therapeutic products in situ, offering unique advantages in antitumor immunotherapy. Through catalytic reactions, both tumor eradication and immune regulation can be simultaneously achieved, favoring the development of systemic antitumor immunity. In recent years, with advancements in catalytic chemistry and nanotechnology, catalytic nanomedicines based on nanozymes, photocatalysts, sonocatalysts, Fenton catalysts, electrocatalysts, piezocatalysts, thermocatalysts and radiocatalysts have been rapidly developed with vast applications in cancer immunotherapy. This review provides an introduction to the fabrication of catalytic nanomedicines with an emphasis on their structures and engineering strategies. Furthermore, the catalytic substrates and state-of-the-art applications of nanocatalysts in cancer immunotherapy have also been outlined and discussed. The relationships between nanostructures and immune regulating performance of catalytic nanomedicines are highlighted to provide a deep understanding of their working mechanisms in the tumor microenvironment. Finally, the challenges and development trends are revealed, aiming to provide new insights for the future development of nanocatalysts in catalytic immunotherapy.
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Nanoestructuras , Neoplasias , Humanos , Nanoestructuras/química , Nanotecnología , Nanomedicina , Neoplasias/tratamiento farmacológico , Inmunoterapia , Microambiente TumoralRESUMEN
The study presents a multifunctional catechol-modified chitosan (Chi-Ca)/oxidized dextran (Dex-CHO) hydrogel (CDP-PB) that possesses antibacterial, antioxidant, and pro-angiogenic properties, aimed at improving the healing of diabetic wounds. The achievement of the as-prepared CDP-PB hydrogel with superb antibacterial property (99.9 %) can be realized through the synergistic effect of phenylboronic acid-modified polyethyleneimine (PEI-PBA) and photothermal therapy (PTT) of polydopamine nanoparticles loaded with the nitric oxide (NO) donor BNN6 (PDA@BNN6). Notably, CDP-PB hydrogel achieves â¼3.6 log10 CFU/mL MRSA of inactivation efficiency under 808 nm NIR laser irradiation. In order to mitigate oxidative stress, the Chi-Ca was synthesized and afterward subjected to a reaction with Dex-CHO via a Schiff-base reaction. The catechol-containing hydrogel demonstrated its effectiveness in scavenging DPPH, â¢OH, and ABTS radicals (> 85 %). In addition, the cellular experiment illustrates the increased migration and proliferation of cells by the treatment of CDP-PB hydrogel in the presence of oxidative stress conditions. Moreover, the findings from the animal model experiments provide evidence that the CDP-PB hydrogel exhibited efficacy in the eradication of wound infection, facilitation of angiogenesis, stimulation of granulation, and augmentation of collagen deposition. These results indicate the potential of the CDP-PB hydrogel for use in clinical applications.
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Quitosano , Diabetes Mellitus , Staphylococcus aureus Resistente a Meticilina , Animales , Antioxidantes/farmacología , Óxido Nítrico , Hidrogeles/farmacología , Dextranos , Cicatrización de Heridas , Catecoles , Antibacterianos/farmacologíaRESUMEN
The non-noble-metal catalysed-multicomponent reactions between flue gas CO2 and cheap industrial raw stocks into high value-added fine chemicals is a promising manner for the ideal CO2 utilization route. To achieve this, the key fundamental challenge is the rational development of highly efficient and facile reaction pathway while establishing compatible catalytic system. Herein, through the stepwise solvent-assisted linker installation, post-synthetic fluorination and metalation, we report the construction of a series of perfluoroalkyl-decorated noble-metal-free metal-organic frameworks (MOFs) PCN-(BPY-CuI)-(TPDC-Fx ) [BPY=2,2'-bipyridine-5,5'-dicarboxylate, TPDC-NH2 =2'-amino-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid] that can catalyze the one-pot four-component reaction between alkyne, aldehyde, amine and flue gas CO2 for the preparation of 2-oxazolidinones. Such assembly endows the MOFs with superhydrophobic microenvironment, superior water resistance and highly stable catalytic site, leading to 21 times higher turnover numbers than that of homogeneous counterparts. Mechanism investigation implied that the substrates can be efficiently enriched by the MOF wall and then the adsorbed amine species act as an extrinsic binding site towards dilute CO2 through their strong preferential formation to carbamate acid. Moreover, density functional theory calculations suggest the tetrahedral geometry of Cu in MOF offers special resistance towards amine poisoning, thus maintaining its high efficiency during the catalytic process.
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The immune checkpoint blockade (ICB) antibody immunotherapy has demonstrated clinical benefits for multiple cancers. However, the efficacy of immunotherapy in tumors is suppressed by deficient tumor immunogenicity and immunosuppressive tumor microenvironments. Pyroptosis, a form of programmed cell death, can release tumor antigens, activate effective tumor immunogenicity, and improve the efficiency of ICB, but efficient pyroptosis for tumor treatment is currently limited. Herein, we show a mild hyperthermia-enhanced pyroptosis-mediated immunotherapy based on hollow carbon nanozyme, which can specifically amplify oxidative stress-triggered pyroptosis and synchronously magnify pyroptosis-mediated anticancer responses in the tumor microenvironment. The hollow carbon sphere modified with iron and copper atoms (HCS-FeCu) with multiple enzyme-mimicking activities has been engineered to induce cell pyroptosis via the radical oxygen species (ROS)-Tom20-Bax-Caspase 3-gasdermin E (GSDME) signaling pathway under light activation. Both in vitro and in vivo antineoplastic results confirm the superiority of HCS-FeCu nanozyme-induced pyroptosis. Moreover, the mild photothermal-activated pyroptosis combining anti-PD-1 can enhance antitumor immunotherapy. Theoretical calculations further indicate that the mild photothermal stimulation generates high-energy electrons and enhances the interaction between the HCS-FeCu surface and adsorbed oxygen, facilitating molecular oxygen activation, which improves the ROS production efficiency. This work presents an approach that effectively transforms immunologically "cold" tumors into "hot" ones, with significant implications for clinical immunotherapy.
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Hipertermia Inducida , Neoplasias , Humanos , Piroptosis , Especies Reactivas de Oxígeno , Inmunoterapia , Carbono , Oxígeno , Microambiente Tumoral , Línea Celular TumoralRESUMEN
Artificial cells are constructed from synthetic materials to imitate the biological functions of natural cells. By virtue of nanoengineering techniques, artificial cells with designed biomimetic functions provide alternatives to natural cells, showing vast potential for biomedical applications. Especially in cancer treatment, the deficiency of immunoactive macrophages results in tumor progression and immune resistance. To overcome the limitation, a BaSO4@ZIF-8/transferrin (TRF) nanomacrophage (NMΦ) is herein constructed as an alternative to immunoactive macrophages. Alike to natural immunoactive macrophages, NMΦ is stably retained in tumors through the specific affinity of TRF to tumor cells. Zn2+ as an "artificial cytokine" is then released from the ZIF-8 layer of NMΦ under tumor microenvironment. Similar as proinflammatory cytokines, Zn2+ can trigger cell anoikis to expose tumor antigens, which are selectively captured by the BaSO4 cavities. Therefore, the hierarchical nanostructure of NMΦs allows them to mediate immunogenic death of tumor cells and subsequent antigen capture for T cell activation to fabricate long-term antitumor immunity. As a proof-of-concept, the NMΦ mimics the biological functions of macrophage, including tumor residence, cytokine release, antigen capture and immune activation, which is hopeful to provide a paradigm for the design and biomedical applications of artificial cells.
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Designing nanozymes that match natural enzymes have always been an attractive and challenging goal. In general, researchers mainly focus on the construction of metal centers and the control of non-metallic ligands of nanozyme to regulate their activities. However, this is not applicable to lactate oxidase, i.e., flavoenzymes with flavin mononucleotide (FMN)-dependent pathways. Herein, we propose a coordination strategy to mimic lactate oxidase based on engineering the electronic properties at the N center by modulating the Co number near N in the Cox-N nanocomposite. Benefitting from the manipulated coordination fields and electronic structure around the electron-rich N sites, Co4N/C possesses a precise recognition site for lactate and intermediate organization and optimizes the absorption energies for intermediates, leading to superior oxidation of the lactate α-C-sp(3)-H bond toward ketone. The optimized nanozyme delivers much improved anticancer efficacy by reversing the high lactate and the immunosuppressive state of the tumor microenvironment, subsequently achieving excellent tumor growth and distant metastasis inhibition. The developed Co4N/C NEs open a new window for building a bridge between chemical catalysis and biocatalysis.
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Ácido Láctico , Neoplasias , Humanos , Nitrógeno , Oxigenasas de Función Mixta/química , Neoplasias/tratamiento farmacológico , Catálisis , Microambiente TumoralRESUMEN
Catalytic nanomedicine can in situ catalytically generate bactericidal species under external stimuli to defend against bacterial infections. However, bacterial biofilms seriously impede the catalytic efficacy of traditional nanocatalysts. In this work, MoSe2 nanoflowers (NFs) as piezoelectric nanozymes were constructed for dual-driven catalytic eradication of multi-drug-resistant bacterial biofilms. In the biofilm microenvironment, the piezoelectricity of MoSe2 NFs was cascaded with their enzyme-mimic activity, including glutathione oxidase-mimic and peroxidase-mimic activity. As a result, the oxidative stress in the biofilms was sharply elevated under ultrasound irradiation, achieving a 4.0 log10 reduction of bacterial cells. The in vivo studies reveal that the MoSe2 NFs efficiently relieve the methicillin-resistant Staphylococcus aureus bacterial burden in mice under the control of ultrasound at a low power density. Moreover, because of the surface coating of antioxidant poly(ethyleneimine), the dual-driven catalysis of MoSe2 NFs was retarded in normal tissues to minimize the off-target damage and favor the wound healing process. Therefore, the cascade of piezoelectricity and enzyme-mimic activity in MoSe2 NFs reveals a dual-driven strategy for improving the performance of catalytic nanomaterials in the eradication of bacterial biofilms.
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Herein, the covalently connected core-shell metal-organic frameworks (MOFs)@covalent-organic frameworks (COFs) hybrid materials were successfully constructed by coating the stable COF-OH shell on the NH2-MIL-125 core. The introduction of the NH2-MIL-125 core endowed the hybrid materials with high Brunauer-Emmett-Teller (BET) surface area (SBET) and abundant unsaturated metal sites. And the coating of COF-OH shell endowed the hybrid materials outstanding physicochemical stability and visible-light response, and suitable band gaps. Moreover, the thickness of the COF-OH shell was carefully adjusted according to the feeding amount of NH2-MIL-125. Impressively, the electron transfer pathway in the formed heterostructure was clarified and it was proven that a type-II heterojunction was generated between the MOFs and the COFs. The formed stable CN covalent bonds in the interfacial layer was beneficial to the photogenerated electron transfer and the electron-hole pairs separation, which greatly enhanced the CO2 photocatalytic reduction. The product NH2-MIL-125@COF-3 exhibited the highest CO yield of 22.93 µmol·g-1·h-1, about 2 times higher than NH2-MIL-125 (11.82 µmol·g-1·h-1) and 3 times greater than COF-OH (7.26 µmol·g-1·h-1). This work can provide helpful ideas for the careful design of the novel MOFs@COFs hybrid materials as well as useful exploration for the CO2 photocatalytic reduction.
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Precise catalysis is pursued for the biomedical applications of artificial enzymes. It is feasible to precisely control the catalysis of artificial enzymes via tunning the temperature-dependent enzymatic kinetics. The safety window of cold temperatures (4-37 °C) for the human body is much wider than that of thermal temperatures (37-42 °C). Although the development of cold-activated artificial enzymes is promising, there is currently a lack of suitable candidates. Herein, a cold-activated artificial enzyme is presented with Bi2Fe4O9 nanosheets (NSs) as a paradigm. The as-obtained Bi2Fe4O9 NSs possess glutathione oxidase (GSHOx)-like activity under cold temperature due to their pyroelectricity. Bi2Fe4O9 NSs trigger the cold-enzymatic death of tumor cells via apoptosis and ferroptosis, and minimize the off-target toxicity to normal tissues. Moreover, an interventional device is fabricated to intelligently and remotely control the enzymatic activity of Bi2Fe4O9 NSs on a smartphone. With Bi2Fe4O9 NSs as an in situ vaccine, systemic antitumor immunity is successfully activated to suppress tumor metastasis and relapse. Moreover, blood biochemistry analysis and histological examination indicate the high biosafety of Bi2Fe4O9 NSs for in vivo applications. This cold nanozyme provides a strategy for cancer vaccines, which can benefit the precise control over catalytic nanomedicines.
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Frío , Neoplasias , Humanos , Temperatura , Nanomedicina , Catálisis , Neoplasias/tratamiento farmacológicoRESUMEN
Nanodrugs are becoming increasingly important in the treatment of bacterial infection, but their low penetration ability to bacterial biofilm is still the main challenge hindering their therapeutic effect. Herein, nitric oxide (NO)-driven nanomotor based on L-arginine (L-Arg) and gold nanoparticles (AuNPs) loaded dendritic mesoporous silica nanoparticles (AG-DMSNs) is fabricated. AG-DMSNs have the characteristics of cascade catalytic reaction, where glucose is first catalyzed by the asymmetrically distributed AuNPs with their glucose oxidase (GOx)- mimic property, which results in unilateral production of hydrogen peroxide (H2 O2 ). Then, L-Arg is oxidized by the produced H2 O2 to release NO, leading to the self-propelled movement. It is found that the active movement of nanomotor promotes the AG-DMSNs ability to penetrate biofilm, thus achieving good biofilm clearance in vitro. More importantly, AG-DMSNs nanomotor can eliminate the biofilm of methicillin-resistant Staphylococcus aureus (MRSA) in vivo without causing damage to normal tissues. This nanomotor provides a new platform for the treatment of bacterial infections.
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Infecciones Bacterianas , Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Humanos , Óxido Nítrico , Oro/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Biopelículas , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
Catalytic nanomedicine with the innate features of catalysts brings incomparable properties to biomedicine over traditional drugs. The temperature-dependent activity of catalysts provides catalytic nanomedicines with a facile strategy to control their therapeutic performance. Tuning catalytic nanomedicine by cold treatment (4-37 °C) is safe and desired for practical applications, but there is a lack of cold-catalytic platforms. Herein, with black phosphorus (BP) as a model pyroelectric nanocatalyst, we explored the potential of cold-catalysts for antitumor therapy. BP nanosheets with pyro-catalytic activity catalyze the generation of oxidative stress to activate antitumor immunity under cold treatment. Due to the cold-catalytic immunomodulation, immune memory was successfully achieved to prevent tumor metastasis and recurrence. Considering the safety and conductive depth (>10 mm) of cold in the body, pyroelectric nanocatalysts open up exciting opportunities for the development of cold-catalytic nanomedicine.
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Catalytic nanomedicine, especially artificial enzymes, exhibit obvious merits over traditional nanomedicine. However, the lack of controllability over an enzymatic process seriously challenges the therapeutic performance. Herein, we present a concept of using piezoelectric enzymes in combination with biocomputation ability. As a paradigm, MnTiO3 nanodisks were prepared with multiple enzyme-mimicking activity, including glutathione oxidase, peroxidase, and catalase. Different from the conventional artificial enzymes, the enzymatic activity of MnTiO3 nanodisks was activated by ultrasound and switched by a tumor microenvironment, which allows precise control over enzymatic catalysis in tumors. By virtue of the multiple artificial enzyme activity of MnTiO3 nanodisks, a biocomputing platform was constructed based on a Boolean logic-based algorithm. With ultrasound and tumor microenvironment as input signals, cytotoxicity was output via logic-based biocomputation for programed tumor killing. The concept of piezoelectric enzymes together with a biocomputation strategy provides an intelligent and effective approach for catalytic tumor eradication.
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Neoplasias , Humanos , Catálisis , Enzimas , Lógica , Nanomedicina , Microambiente TumoralRESUMEN
Iron, nitrogen-codoped carbon (Fe-N-C) nanocomposites have emerged as viable electrocatalysts for the oxygen reduction reaction (ORR) due to the formation of FeNx Cy coordination moieties. In this study, results from first-principles calculations show a nearly linear correlation of the energy barriers of key reaction steps with the Fe magnetic moment. Experimentally, when single Cu sites are incorporated into Fe-N-C aerogels (denoted as NCAG/Fe-Cu), the Fe centers exhibit a reduced magnetic moment and markedly enhanced ORR activity within a wide pH range of 0-14. With the NCAG/Fe-Cu nanocomposites used as the cathode catalyst in a neutral/quasi-solid aluminum-air and alkaline/quasi-solid zinc-air battery, both achieve a remarkable performance with an ultrahigh open-circuit voltage of 2.00 and 1.51â V, large power density of 130 and 186â mW cm-2 , and good mechanical flexibility, all markedly better than those with commercial Pt/C or Pt/C-RuO2 catalysts at the cathode.
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The tumor microenvironment (TME) featured by immunosuppression and hypoxia is pivotal to cancer deterioration and metastasis. Thus, regulating the TME to improve cancer cell ablation efficiency has received extensive interest in oncotherapy. However, to reverse the immunosuppression and alleviate hypoxia simultaneously in the TME are major challenges for effective cancer therapy. Herein, a multifunctional platform based on Au nanoparticles and a carbon dots modified hollow black TiO2 nanosphere (HABT-C) with intrinsic cascade enzyme mimetic activities is prepared for reversing immunosuppression and alleviating hypoxia in the TME. The HABT-C NPs possess triple-enzyme mimetic activity to act as self-cascade nanozymes, which produce sufficient oxygen to alleviate hypoxia and generate abundant ROS. The theoretical analysis demonstrates that black TiO2 facilitates absorption of H2O and O2, separation of electron-holes, and generation of ROS, consequently amplifying the sonodynamic therapy (SDT) efficiency. Specifically, HABT-C exhibits favorable inhibition of immunosuppressive mediator expression, along with infiltrating of immune effector cells into the TME and reversing the immunosuppression in the TME. As a result, HABT-C can effectively kill tumor cells via eliciting immune infiltration, alleviating hypoxia, and improving SDT efficiency. This cascade nanozyme-based platform (HABT-C@HA) will provide a strategy for highly efficient SDT against cancer by modulation of hypoxia and immunosuppression in the TME.
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Nanopartículas del Metal , Nanopartículas , Neoplasias , Humanos , Especies Reactivas de Oxígeno/metabolismo , Oro/farmacología , Nanopartículas del Metal/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Hipoxia , Microambiente Tumoral , Oxígeno/metabolismo , Terapia de Inmunosupresión , Línea Celular TumoralRESUMEN
Regulation of angiogenesis is a great challenge for effective anticancer therapy. Generally, anti-angiogenic therapies are focused on inhibition of inducers involved in pro-angiogenic communication pathways. Despite the great potential of anti-angiogenic therapy, engineering efficient angiogenesis inhibition agents (AIAs) is still a formidable challenge, since most anti-angiogenic therapies are limited due to the cancer recurrence via compensatory expression of different angiogenic mediators. Herein, we present a new strategy of near-infrared-II (NIR-II) responsive hydrogel AIAs, constructed by incorporation of nitric oxide (NO) precursor (BNN6) and 2D WO2.9 nanosheets within hydrogel (WB@hydrogel). Because of the defect/2D engineering, the bandgap of the WO2.9 nanosheets narrows, which extends the absorption to the NIR-II region. It offers a favorable NIR-II controlled manner for NO generation through irradiation time and light intensity. The continuous supply of NO can activate the expression of wild-type p53 protein and further reverse the transcriptional expression of pro- and anti-angiogenic factors of the tumor microenvironment (TME), subsequently alternating pro-angiogenic TME to anti-angiogenic TME. In the murine tumor model, this method achieved high tumor growth inhibition (TGI) rate and excellent anti-recurrence efficiency.
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Hidrogeles , Neoplasias , Animales , Ratones , Óxido Nítrico , Microambiente TumoralRESUMEN
Chemical messengers have been recognized as signaling molecules involved in regulating various physiological and metabolic activities. Nevertheless, they usually show limited regulatory efficiency due to the complexity of biological processes. Especially for tumor cells, antideath pathways and tumor metastasis are readily activated to resist chemical messenger regulation, further impairing antitumor outcomes. Therefore, it is imperative to develop strategies for tumor eradication with chemical messengers. Herein, a nanomessenger was prepared with signaling transduction cascades to amplify the regulatory activity of chemical messengers and mediate antitumor immunotherapy. Ca2+ and H2S as two chemical messengers were released from nanomessengers to synergistically elevate intracellular Ca2+ stress and mediate subsequent cell death. Meanwhile, zinc protoporphyrin (ZnPP) as a messenger amplifier suppressed the antideath effect of tumor cells. As a result, tumor cells underwent Ca2+-dependent cell death via signaling transduction cascades to release tumor-associated antigens, which further served as an in situ tumor vaccine to activate antitumor immunity. In vivo studies revealed that both primary tumors and distant metastases were markedly eradicated. Furthermore, immunological memory was fabricated to arrest tumor metastasis and recurrence. This work introduces cascade engineering into chemical messengers and thus offers a strategy for amplifying chemical messenger-mediated cellular regulation, which would promote the future development of chemical messenger-mediated immunotherapy.Ì.
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Inmunoterapia , Neoplasias , Humanos , Transducción de Señal , Neoplasias/terapia , Memoria Inmunológica , Muerte Celular , Factores InmunológicosRESUMEN
Stanene (Sn)-based materials have been extensively applied in industrial production and daily life, but their potential biomedical application remains largely unexplored, which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials. Herein, we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional (2D) Sn nanosheets (SnNSs). The obtained SnNSs exhibited a typical sheet-like structure with an average size of ~ 100 nm and a thickness of ~ 5.1 nm. After PEGylation, the resulting PEGylated SnNSs (SnNSs@PEG) exhibited good stability, superior biocompatibility, and excellent photothermal performance, which could serve as robust photothermal agents for multi-modal imaging (fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer. Furthermore, we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs, revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal. This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics. This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications.
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Piezoelectric materials, with their unique ability for mechanical-electrical energy conversion, have been widely applied in important fields such as sensing, energy harvesting, wastewater treatment, and catalysis. In recent years, advances in material synthesis and engineering have provided new opportunities for the development of bio-piezoelectric materials with excellent biocompatibility and piezoelectric performance. Bio-piezoelectric materials have attracted interdisciplinary research interest due to recent insights on the impact of piezoelectricity on biological systems and their versatile biomedical applications. This review therefore introduces the development of bio-piezoelectric platforms from a broad perspective and highlights their design and engineering strategies. State-of-the-art biomedical applications in both biosensing and disease treatment will be systematically outlined. The relationships between the properties, structure, and biomedical performance of the bio-piezoelectric materials are examined to provide a deep understanding of the working mechanisms in a physiological environment. Finally, the development trends and challenges are discussed, with the aim to provide new insights for the design and construction of future bio-piezoelectric materials.
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Materiales Biocompatibles , Electricidad , Ingeniería de TejidosRESUMEN
Conjugated porous polymers with rapid separation of photogenerated charges and multiple catalytic pathways remain a great challenge. Herein, two ferrocene-based polymers (Fc-CPPs) with high charge separation efficiency and unique dual catalytic routes for Cr(vi) reduction were developed. They exhibited an excellent efficiency, with almost 99% of Cr(vi) readily converted to Cr(iii) under 15 min of visible light illumination (λ > 420 nm).
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An injectable gellan gum-based nanocomposite hydrogel (Bi2S3@GG) was designed for X-ray computed tomography (CT) imaging and photothermal/antiangiogenic therapy. The linear anionic polysaccharide gellan gum (GG) was used as a stabilizer, embedded with ultra-small bismuth sulfide (Bi2S3) nanodots (â¼2 nm) through a one-pot synthesis method. The as-prepared Bi2S3@GG hydrogel displays excellent capability for both photothermal therapy (PTT) (with a photothermal conversion efficiency of 44.3%) and X-ray computed tomography (with an X-ray absorption coefficient of 51.5 HU L g-1), integrated with real-time monitoring drug retention and tunable therapeutic functions. After the incorporation of sorafenib (SF), the hydrogel shows a sustained release of SF over 15 days. A tumor suppression rate of 98.2% is shown at day 22 postinjection in the mice received the combined treatments of photothermal/antiangiogenic therapy. In contrast, tumor growth and recurrence are observed in the single treatment. Our work presents a new strategy to construct a multifunctional hydrogel platform for a safe and precise antitumor therapy.