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Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.
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Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Imunoterapia , Oxaliplatina , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/terapia , Oxaliplatina/uso terapêutico , Oxaliplatina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Imunoterapia/métodos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Masculino , Feminino , Prognóstico , Pessoa de Meia-IdadeRESUMO
A simple penicillinase functionalized two-dimensional photonic crystal hydrogel (2DPPCH) biosensor was developed for colorimetric detection of penicillin G and penicillinase inhibitors. The penicillinase can specifically recognize penicillin G and catalyze it to produce penicilloic acid, which decreases the pH of the hydrogel microenvironment and shrinks the pH-sensitive hydrogel. The particle spacing decrease of the 2D photonic crystal array induced by the hydrogel shrinkage further causes a blue-shift in the diffraction wavelength. While the hydrolysis reaction is repressed upon treatment with clavulanate potassium (a kind of penicillinase inhibitor), no significant change in the diffraction wavelength is found. The detection of targets can be achieved by measuring the Debye diffraction ring diameter or observing the structural color change in the visible region. The lowest detectable concentrations for penicillin G and clavulanate potassium are 1 µM and 0.1 µM, respectively. Moreover, the 2DPPCH is proved to exhibit high selectivity and an excellent regeneration property, and it shows satisfactory performance for penicillin G analysis in real water samples.
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Técnicas Biossensoriais/métodos , Hidrogéis/química , Penicilina G/análise , Penicilinase/metabolismo , Fótons , Inibidores de beta-Lactamases/análise , Inibidores de beta-Lactamases/farmacologiaRESUMO
Rational design of stimuli-responsive polymers for cytosolic protein delivery with robust efficiency is of great importance but remains a challenging task. Here, we reported a bioreducible and amphiphilic dendrimer bearing a fluoroalkyl tail for this purpose. The fluorolipid was conjugated to the focal point of a cysteamine-cored polyamidoamine dendrimer via disulfide bond, while phenylboronic acid moieties were decorated on dendrimer surface for efficient protein binding. The yielding polymer showed high protein binding capability and complex stability and could efficiently release the cargo proteins in a glutathione-responsive manner. The designed polymer was effective in the delivery of various membrane-impermeable proteins into living cells with reserved bioactivities. In addition, the polymer efficiently delivered a toxin protein saporin into 4T1 breast cancer cells and inhibited the tumor growth in vivo after intravenous injection. The developed polymer in this study is a promising vector for the delivery of membrane-impermeable proteins to treat various diseases.
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Dendrímeros , Linhagem Celular Tumoral , Citosol , Polímeros , ProteínasRESUMO
Numerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs; however, the complexities in carrier materials and functional integration make it challenging to promote these candidates for clinical translation. In this study, a facile method to prepare carrier-free anticancer nanodrug with inherent bone targeting and osteoclastogenesis inhibition capabilities is reported. Phytic acid, a naturally occurring and nontoxic product, is reacted with cisplatin to form uniform nanoparticles of different sizes. The prepared nanoparticles possess high drug loading and pH-responsive drug release behaviors. Phytic acid in the nanomedicine ensures high bone targeting and osteoclastogenesis inhibition, and the released platinum drugs triggered by tumor extracellular acidity eradicate tumor cells. The nanomedicine around 100 nm shows high anticancer activity and much reduced side effects in a subcutaneous breast cancer model when compared with cisplatin. In addition, it shows high accumulation at osteolytic lesions, and efficiently inhibits tumor growth and tumor-associated osteolysis in a bone metastatic breast cancer model. Here, a facile and efficient strategy to prepare carrier-free nanomedicines with high anticancer drug loading, inherent bone targeting, and osteoclast inhibitory activities for cancer therapy is provided.
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Antineoplásicos , Nanopartículas , Neoplasias , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico , PlatinaRESUMO
As an effective nuclear energy resource, uranium plays an important role in industry and energy but the wastes of uranium also cause radioactive contamination, which is harmful to the environment and the human body. Herein, a responsive photonic crystal (PC) film sensor for the ultrasensitive and label-free detection of uranyl ions (UO22+) has been proposed, which is easy to construct and does not need to be combined with a hydrogel. The PC film is not pH-sensitive because it is obtained by the self-assembly of methyl methacrylate-acrylonitrile co-polymeric nanospheres (PMMA-AN). These nanospheres were modified with amidoxime groups, which have a good coordination ability with UO22+. The bindings between nanospheres and UO22+ change the refractive index and disturb the face-centered cubic structure of the film, which leads to a decrease in the diffraction peak intensity of the PC film. The sensor works in the concentration range of 10 pM to 100 µM for UO22+ determination and the decreased intensities of the diffraction peaks are linearly correlated with the logarithm of UO22+ concentration in the range from 1 nM to 100 µM. Moreover, the sensor shows good selectivity for UO22+ and can also perform the determination of UO22+ in a real sample. The responsive PC film sensor shows great potential in the label-free and ultrasensitive detection of UO22+.
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Bortezomib (BTZ) is a first-in-class boronate proteasome inhibitor used for cancer therapy, but its therapeutic efficacy is usually inhibited by dietary polyphenols due to boronate-catechol complexation. Benefiting from such dynamic covalent chemistry, herein we describe a novel class of supramolecular nanomedicines by rationally converting natural polyphenols from foe to friend through polyphenol-mediated BTZ assembly strategy. The simple conjugation of BTZ to catechol-containing natural polyphenols via boronate ester bond allows the facile formation of dynamic drug amphiphiles, with pH-dependent assembly/disassembly behaviors under different physiological conditions. Ferric ion was also incorporated into the supramolecular system via metal-phenolic coordination interaction to both introduce bioimaging function and facilitate stability of the supramolecular nanomedicines. Our investigation revealed that the supramolecular nanomedicine consisting of natural polyphenol, BTZ and ferric ion dramatically induced apoptosis on cancer cells and suppressed tumor growth in both subcutaneous and bone tumor models with limited adverse effects. Such natural polyphenol-mediated small drug assembly strategy enables the robust fabrication of supramolecular nanomedicines for efficient delivery and controlled release of BTZ in targeted tumor sites, which could be further employed in other types of boronic acid-containing supramolecular therapeutics toward a wide range of diseases.
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Engineering near-infrared (NIR) light-sensitive enzymes remains a huge challenge. A photothermal effect-associated method is developed for tailoring the enzymatic activity of enzymes by exposure to NIR light. An ultrasmall platinum nanoparticle was anchored in an enzyme to generate local heating upon NIR irradiation, which enhanced the enzyme activity without increasing bulk temperature. Following NIR irradiation, the enzyme activity was tailored rapidly and reversibly, and was modulated by varying laser power density and irradiation time. Four enzymes were engineered, including glucoamylase, glucose oxidase, catalase, and proteinaseâ K with NIR-light sensitivity, and demonstrated their utility in practical applications such as photolithography and NIR light-responsive antibacterial or anticancer actions. Our investigation suggests that this approach could be broadly used to engineer enzymes with NIR-light sensitivity for many biological applications.
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Enzimas/metabolismo , Raios Infravermelhos , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Catalase/metabolismo , Endopeptidase K/metabolismo , Glucana 1,4-alfa-Glucosidase/metabolismo , Glucose Oxidase/metabolismo , Nanopartículas Metálicas/química , Platina/química , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Bone metastasis is a frequent and fatal complication of cancer that lacks effective clinical treatment. Photothermal therapy represents a new strategy for the destruction of multiple cancers. In this study, trifolium-like platinum nanoparticles (TPNs) with small size and excellent photothermal conversion property are prepared via a facile and green method. TPNs show minimal cytotoxicity on normal cell lines and kill cancer cells upon exposure to a near-infrared light. These nanoparticles effectively inhibit tumor growth and prevent osteolysis in a bone metastasis model. This study offers a promising strategy in the treatment of bone metastasis.
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Neoplasias Ósseas/terapia , Nanopartículas Metálicas/química , Osteólise/fisiopatologia , Fototerapia/métodos , Platina/química , Trifolium/química , Animais , Materiais Biocompatíveis/química , Peso Corporal , Neoplasias Ósseas/secundário , Linhagem Celular , Linhagem Celular Tumoral , Células HeLa , Humanos , Imageamento Tridimensional , Raios Infravermelhos , Camundongos , Camundongos Nus , Microscopia Eletrônica de Transmissão , Células NIH 3T3 , Metástase Neoplásica , Neoplasias/patologia , Fotoquímica , Compostos de Platina/química , Povidona/química , Tomografia Computadorizada por Raios X , Microtomografia por Raio-XRESUMO
Periodontitis is a chronic inflammatory disease characterized by plaque accumulation, resulting in immune microenvironment disorders and resorption of alveolar bone. To promote bone healing under inflammatory environments, a functional biomaterial based on disease pathophysiology is designed. A novel fatty acid C10-modified polypeptide, C10-KR8, is discovered to have excellent abilities in modulating macrophage repolarization and promoting bone regeneration in periodontitis. To build a multifunctional material localized drug delivery system, C10-KR8@ZIF-8 (C10-KR8-loaded zeolitic imidazolate framework-8) nanoparticles are constructed to sustainedly release the C10-KR8 peptide and Zn elements. By synergistic effects of providing a dynamic immuno-modulatory environment and promoting osteogenesis under pathological conditions, the obtained pH-responsive nanoparticles display excellent bone regeneration capability. Furthermore, coimmunoprecipitation/liquid chromatography-tandem mass spectrometry analysis and proteomics analysis revealed that the C10-KR8 peptide directly interacts with the high-temperature requirement protein A1 (Htra1), and C10-KR8@ZIF-8 nanoparticles promote the osteogenic differentiation of bone mesenchymal stem cells by activating the focal adhesion kinase (FAK)/phosphatidylinositide 3-kinase (PI3K)/AKT pathway and enhancing the nuclear localization of Yes-associated protein (YAP). Taken together, this study demonstrates C10-KR8 peptide regulate osteoimmunology and bone regeneration by Htra1/FAK/YAP pathway and that ZIF-8-based peptide loading platform is a promising strategy for periodontitis.
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With increasing age, there is a notable increase in the differentiation of bone marrow-derived mononuclear cells (BMMs) into osteoclasts, accompanied by a concurrent rise in both osteoclast quantity and activity. This escalation in osteoclastic activity accelerates bone resorption, which in turn contributes to age-related bone loss and metabolic bone disorders, notably osteoporosis. Our study confirms that elevated IL-19 expression promotes aging-induced bone loss in aged mice and sheds light on the regulatory mechanisms upstream of IL-19 expression and secretion. Primarily, it is the methylation status of the IL-19 gene's promoter region that impacts Atonal BHLH Transcription Factor 1 (Atoh1)'s ability to bind to the promoter. We found that this specific mechanism involves reduced expression and binding affinity of Dnmt1 to the IL-19 promoter region. The findings of our study suggest that targeting IL-19 could be a potential strategy for managing bone loss-related conditions and enhance the current understanding of how DNA methylation levels contribute to age-related bone loss.
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BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Prognóstico , Biomarcadores , Imunoterapia , Microambiente Tumoral/genética , Complexo IV da Cadeia de Transporte de ElétronsRESUMO
Rational design of efficient cytosolic protein delivery carriers holds enormous promise for biotherapeutics development. Several delivery systems have been developed during the past decades, while tailoring the balance between extracellular protein binding and intracellular cargo release is still challenging. In this study, we synthesized a series of oxygen-sensitive reactive polymers, rich in boron, by radical polymerization and post-modification for cytosolic protein delivery in vitro and in vivo. The introduction of boronate building blocks into the polymer scaffold significantly enhanced its protein binding affinity, and the polymer/protein complexes with high stability were obtained by tailoring the molecular ratios between the boronate ligands and the amine groups. The lead material screened from the polymer library exhibited efficient protein delivery efficacy that can release cargo proteins in cytosol in a reactive oxygen species responsive manner, which enables intracellular delivery of proteins with maintained bioactivity. In addition, the polymer-based nanoformulations efficiently delivered saporin, a toxin protein, into osteosarcoma cells and tumor tissues, and exhibited high therapeutic efficacy in an osteosarcoma mouse model. The synthesized polymer in this study can be developed as a promising nanocarrier for cytosolic delivery of protein therapeutics to treat a variety of diseases.
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Osteossarcoma , Polímeros , Animais , Camundongos , Polímeros/química , Portadores de Fármacos/química , Espécies Reativas de Oxigênio , ProteínasRESUMO
Development of intracellular delivery systems for bioactive peptides remains challenging. Herein, we report a facile strategy to address this issue by conjugating peptides with benzaldehyde-tethered fluorous tags to generate dynamic peptide amphiphiles via a hydrazone bond for efficient cytosolic delivery. Those dynamic peptide fluoroamphiphiles could self-assemble into nanoparticles that readily cross the cell membrane. Using this strategy, several bioactive peptides were efficiently internalized by cancer cells and released into the cytosol to exert their biological functions, which showed much higher efficacies than non-fluorous lipids and cell penetrating peptide decorated peptides. Moreover, the fluorous tagged proapoptotic peptide was able to efficiently inhibit tumor growth in vivo. This report provides a new family of fluorous tags based on benzaldehyde for efficient cytosolic peptide delivery.
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Peptídeos Penetradores de Células , Nanopartículas , Citosol/metabolismo , Benzaldeídos , Peptídeos Penetradores de Células/metabolismo , Nanopartículas/químicaRESUMO
Poly(α-L-glutamic acid) (PGA) is a class of synthetic polypeptides composed of the monomeric unit α-L-glutamic acid. Owing to their biocompatibility, biodegradability, and non-immunogenicity, PGA-based nanomaterials have been elaborately designed for drug delivery systems. Relevant studies including the latest research results on PGA-based nanomaterials for drug delivery have been discussed in this work. The following related topics are summarized as: (1) a brief description of the synthetic strategies of PGAs; (2) an elaborated presentation of the evolving applications of PGA in the areas of drug delivery, including the rational design, precise fabrication, and biological evaluation; (3) a profound discussion on the further development of PGA-based nanomaterials in drug delivery. In summary, the unique structures and superior properties enables PGA-based nanomaterials to represent as an enormous potential in biomaterials-related drug delivery areas.
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Nanoestruturas , Ácido Poliglutâmico , Sistemas de Liberação de Medicamentos , Ácido GlutâmicoRESUMO
This study aims to investigate the effects of different selenium (Se) sources on the growth performance of Chinese broilers and provide a scientific rationale for adding Se additives to broiler feed. Relevant studies that meet standard inclusion criteria were identified and extracted from China National Knowledge Infrastructure and Wanfang and Chinese Scientific Journal (VIP) databases. A total of 9 studies with 539 subjects were included. A meta-analysis was performed with STATA15.0 to estimate the combined standardized mean difference (SMD) with a 95% confidence interval (95% CI). Heterogeneity test of articles was examined by Q-test, and the results showed that P values of feed conversion ratio, average daily gain (ADG), and average daily intake were all less than 0.05, suggesting a strong heterogeneity among the selected literature. Therefore, the random effect model is selected to calculate the SMD of the three indexes. The combined SMDs (95% CI) of feed:gain, ADG, and average daily feed intake (ADFI) were -0.39 (-1.03, 0.25), 0.26 (-0.29, 0.81), and -1.45 (-3.09, 0.20), respectively, and the P values were all less than 0.05. This study shows that the absolute differences in the growth performance (feed:gain, ADG, and ADFI) of broilers fed with either organic or inorganic Se supplements at the same dose were quite small. The P values of Egger's test were 0.770, 0.089, and 0.426, respectively, for the above indexes, showing no significant publication bias. Sensitivity analysis ensured the stability and reliability of the results. In summary, the effects of organic and inorganic Se in feed on the growth performance of broilers are statistically equal.
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Cytosolic delivery of peptides remains a challenging task owing to their susceptibility to enzymatic degradation and the existence of multiple intracellular barriers. Here, we report a new strategy to address these issues by decoration of a fluorous tag on the terminal of cargo peptides. The fluorous-tagged peptides were assembled into nanostructures, efficiently internalized by cells via several endocytic pathways and released into the cytosol after endosomal escape. They were relatively stable against enzymatic degradation and showed much higher efficiency than nonfluorinated analogs and cell penetrant peptide-conjugated ones. The proposed strategy also efficiently delivered a proapoptotic peptide into specific sites in the cells and restored the function of cargo peptide after cytosolic delivery. The fluorous-tagged proapoptotic peptide efficiently inhibited tumor growth in vivo. This study provides an efficient fluorination strategy to promote the cytosolic delivery of peptides.
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Nanoestruturas , Peptídeos , Citosol/metabolismo , Sistemas de Liberação de Medicamentos , Endossomos/metabolismo , Peptídeos/metabolismoRESUMO
Photocleavable hydrogels are of great importance in the field of controlled drug delivery, stem cell fate regulation, surface patterning, and intelligent devices. However, the development of novel photocleavable gel systems by visible light is usually met with challenges such as the lack of efficient and tunable photocleavable groups and reactions. Herein, we reported the facile fabrication of a new type of photocleavable hydrogels by the direct gelation of 4-arm thiol-terminated polyethylene glycol with 3,6-dichloro-1,2,4,5-tetrazine via the formation of S,S-tetrazine linkages. The prepared hydrogels underwent efficient degradation upon irradiation by ultraviolet or green light, and the degradation kinetics could be significantly promoted by hydrogen peroxide. Correspondingly, the hydrogels loaded with calcium peroxide microparticles or glucose oxidase/catalase enzymes enabled the precise and efficient in vivo photocontrol of gel degradation and drug release for cancer treatment. This work offers a promising and facile strategy towards the fabrication of visible light cleavable hydrogels with tunable and on-demand drug release properties.
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Cancer cells are commonly characterized by high cellular oxidative stress and thus have poor tolerance to oxidative insults. In this study, we developed a nano-formulation to elevate the level of reactive oxygen species (ROS) in cancer cells via promoting ROS production as well as weakening cellular anti-oxidizing systems. The nanoagent was fabricated by encapsulating two natural product molecules, cinnamaldehyde (CA) and diallyl trisulfide (DATS), in PLGA-PEG copolymer formulated nanoparticles. CA promotes ROS generation in cancer cells and DATS depletes cellular glutathione. CA and DATS exhibited a synergistic effect in amplifying the ROS levels in cancer cells and further in their combined killing of cancer cells. The in vivo experiments revealed that the CA and DATS-encapsulated nanoagent suppressed tumors more efficiently as compared with the single drug-loaded ones, and the tumor-targeted delivery further enhanced the therapeutic efficacy. This study suggests that the combined enhancement of oxidative stress by CA and DATS could be a promising strategy for cancer therapy.
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Dura injury can be intractable during neurosurgical operations. Dural sealant is effective for aiding dura repair and diminishing postoperative complications. However, a more optimal dural sealant is still clinically required. On the other hand, spinal cord injury (SCI) is a common comorbidity of the dural injury. Exception for surgical decompression, other clinically approved treatment for SCI is still limited. In this study, an elastic gel consisting of natural polyphenol tannic acid (TA) and pluronic F-127 (PF127) was prepared by a facile strategy. Comparing with traditional fibrin glue, the prepared TA-PF127 gel exhibited much higher bonding strength and sealing effect both in vitro and in vivo, and thus effectively prevented postoperative cerebral spinal fluid leakage. Based on a mice severe SCI model of spinal cord transection, the sealing and antioxidant property of TA-PF127 gel effectively decreased the reactive oxygen species production, inhibited neural cells apoptosis and inflammatory response, promoted glial scar formation and restrained lesion zone, maintained neurons and dramatically promoted neurological function recovery of mice after SCI. Due to the simple and biocompatible components in the gel, TA-PF127 has a promising potential to become a novel dural sealant for simultaneous dura sealing and SCI treatment in clinical neurosurgical operations.
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Poloxâmero , Traumatismos da Medula Espinal , Animais , Dura-Máter , Adesivo Tecidual de Fibrina , Camundongos , Polifenóis , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológicoRESUMO
The off-on manipulation of enzyme activity is a challenging task. We report a new strategy for reversible off-on control of enzyme activity by near-infrared light. Enzymes acting on macromolecular substrates are embedded with an ultrasmall platinum nanoparticle and decorated with thermoresponsive copolymers, which exhibit upper critical solution temperature (UCST) behavior. The polymer-enzyme nanohybrids form microscale aggregates in solution below the UCST to prevent macromolecular substrates from approaching the enzymes and thus inhibit the enzyme activity, and they disassemble above the UCST to reactivate the enzyme. Upon near-infrared irradiation, platinum nanoparticles inside the enzymes generate heat through a photothermal effect to cause phase transition of the copolymers. Therefore, we can reversibly switch off and on the activities of three enzymes acting on polysaccharide, protein, and plasmid. The enzyme activities are increased by up to 61-fold after laser irradiation. This study provides a facile and efficient method for off-on control of enzyme activity.