ABSTRACT
Single-atom nanozymes (SAzymes) are emerging natural enzyme mimics and have attracted much attention in the biomedical field. SAzymes with MetalâNx sites designed on carbon matrixes are currently the mainstream in research. It is of great significance to further expand the types of SAzymes to enrich the nanozyme library. Single-atom alloys (SAAs) are a material in which single-atom metal sites are dispersed onto another active metal matrix, and currently, there is limited research on their enzyme-like catalytic performance. In this work, a biodegradable Pt1Pd SAA is fabricated via a simple galvanic replacement strategy, and for the first time reveals its intrinsic enzyme-like catalytic performance including catalase-, oxidase-, and peroxidase-like activities, as well as its photodynamic effect. Experimental characterizations demonstrate that the introduction of single-atom Pt sites contributes to enhancing the affinity of Pt1Pd single-atom alloy nanozyme (SAAzyme) toward substrates, thus exhibiting boosted catalytic efficiency. In vitro and in vivo experiments demonstrate that Pt1Pd SAAzyme exhibits a photo-controlled therapeutic effect, with a tumor inhibition rate of up to 100%. This work provides vital guidance for opening the research direction of SAAs in enzyme-like catalysis.
Subject(s)
Alloys , Alloys/chemistry , Animals , Platinum/chemistry , Humans , Catalysis , Neoplasms/therapy , Neoplasms/drug therapy , Mice , Phototherapy/methodsABSTRACT
Single-atom nanozymes (SAzymes), with well-defined and uniform atomic structures, are an emerging type of natural enzyme mimics. Currently, it is important but challenging to rationally design high-performance SAzymes and deeply reveal the interaction mechanism between SAzymes and substrate molecules. Herein, this work reports the controllable fabrication of a unique Cu-N1S2-centred SAzyme (Cu-N/S-C) via a chemical vapor deposition-based sulfur-engineering strategy. Benefiting from the optimized geometric and electronic structures of single-atom sites, Cu-N/S-C SAzyme shows boosted enzyme-like activity, especially in catalase-like activity, with a 13.8-fold increase in the affinity to hydrogen peroxide (H2O2) substrate and a 65.2-fold increase in the catalytic efficiency when compared to Cu-N-C SAzyme with Cu-N3 sites. Further theoretical studies reveal that the increased electron density around single-atom Cu is achieved through electron redistribution, and the efficient charge transfer between Cu-N/S-C and H2O2 is demonstrated to be more beneficial for the adsorption and activation of H2O2. The as-designed Cu-N/S-C SAzyme possesses an excellent antitumor effect through the synergy of catalytic therapy and oxygen-dependent phototherapy. This study provides a strategy for the rational design of SAzymes, and the proposed electron redistribution and charge transfer mechanism will help to understand the coordination environment effect of single-atom metal sites on H2O2-mediated enzyme-like catalytic processes.
Subject(s)
Hydrogen Peroxide , Neoplasms , Humans , Engineering , Chemical Engineering , Phototherapy , Catalysis , Gases , Neoplasms/therapyABSTRACT
Bacterial pneumonia is the leading cause of death worldwide among all infectious diseases. However, currently available vaccines against fatal bacterial lung infections, e.g., pneumonic plague, are accompanied by limitations, including insufficient antigen-adjuvant co-delivery and inadequate immune stimulation. Therefore, there is an urgent requirement to develop next-generation vaccines to improve the interaction between antigen and adjuvant, as well as enhance the effects of immune stimulation. This study develops a novel amino-decorated mesoporous manganese silicate nanoparticle (AMMSN) loaded with rF1-V10 (rF1-V10@AMMSN) to prevent pneumonic plague. These results suggest that subcutaneous immunization with rF1-V10@AMMSN in a prime-boost strategy induces robust production of rF1-V10-specific IgG antibodies with a geometric mean titer of 315,844 at day 42 post-primary immunization, which confers complete protection to mice against 50 × LD50 of Yersinia pestis (Y. pestis) challenge via the aerosolized intratracheal route. Mechanistically, rF1-V10@AMMSN can be taken up by dendritic cells (DCs) and promote DCs maturation through activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and production of type I interferon. This process results in enhanced antigen presentation and promotes rF1-V10-mediated protection against Y. pestis infection. This manganese-based nanoparticle vaccine represents a valuable strategy for combating fatal bacterial pneumonia.
Subject(s)
Plague Vaccine , Plague , Pneumonia, Bacterial , Vaccines , Mice , Animals , Plague/prevention & control , Nanovaccines , Manganese , Antigens, Bacterial/genetics , Pneumonia, Bacterial/prevention & control , Adjuvants, Immunologic , Bacterial ProteinsABSTRACT
Cancer stem cells (CSCs), a type of cell with self-renewal, unlimited proliferation, and insensitivity to common physical and chemical factors, are the key to cancer metastasis, recurrence, and chemo-resistance. Available CSCs inhibition strategies are mainly based on small molecule drugs, yet are limited by their off-target toxicity. The link between CSCs and non-CSCs interconversion is difficult to sever. In this work, a nanotherapeutic strategy based on MnOx -loaded polydopamine (MnOx /PDA) nanobombs with chemodynamic, photodynamic, photothermal and biodegradation properties to inhibit CSCs and non-CSCs concurrently is reported. The MnOx /PDA nanobombs can directly disrupt the microenvironment and tumorigenic capacity of CSCs by generating hyperthermia, oxidative stress and alleviating hypoxia. The markers of CSCs are subsequently downregulated, leading to the clearance of CSCs. Meanwhile, the synergistic therapy mediated by MnOx /PDA nanobombs can directly ablate the bulk tumor cells, thus cutting off the supply of CSCs transformation. For tumor targeting, MnOx /PDA is coated with macrophage membrane. The final tumor inhibition rate of the synergistic therapy is 70.8% in colorectal cancer (CRC) model. Taken together, the present work may open up the exploration of nanomaterial-based synergistic therapy for the simultaneous elimination of therapeutically resistant CSCs and non-CSCs.
Subject(s)
Hyperthermia, Induced , Neoplasms , Humans , Biomimetics , Neoplasms/drug therapy , Phototherapy , Neoplastic Stem Cells/pathology , Tumor MicroenvironmentABSTRACT
Background: Sleep efficiency of <80% based on actigraphy was defined as insomnia as self-reported difficulty falling asleep or waking up at night three to four times per week. It is known that adequate sleep is very important for human wellbeing, affecting people's work and life, insomnia will seriously damage our daily life. There is no recognized non-drug treatment. Studies have found that Taijiquan has a positive effect on insomnia patients. This systematic review and meta-analysis will evaluate the effect of Taijiquan on insomnia. Methods: To find all randomized controlled trials exploring the effects of Taijiquan on insomnia patients in Chinese and English, eight databases (Pubmed, Embase, Cochrane library, Web of Science, CNKI, CBM, VIP, and Wanfang Data) were searched. The retrieval time is from database construction to October 2021. Searches were conducted in both English and Chinese language. A meta-analysis by mean difference (MD) and 95% confidence interval (CI) was performed with RevMan 5.3. The risk of bias for each study was accounted for according to the Cochrane Handbook. Our primary outcome was Pittsburg Sleep Quality Index. We explored sources of heterogeneity by comparing effect sizes across different types of etiology, country, control group, and intervention type. The protocol was pre-registered with PROSPERO, CRD42021284511. Results: Twenty-one RCTs published between 2004 and 2021 with 2,022 participants were included in this study. Twenty-one randomized controlled studies showed that Tai Chi significantly improved PSQI scores in patients with cancer, muscle fibrosis, and sub-health insomnia [MD = -1.16, 95% CI (-1.62, -0.71), P < 0.01]; There is insufficient evidence of improvement in patients with cerebrovascular disease [MD = -0.54, 95% CI (-1.58, 0.51), P = 0.31]; 8-form, 10-form or 24-form Yang's Taijiquan had the same effect in improving PSQI [MD = -1.33, 95% CI (-1.85, -0.81), P < 0.01]. When there is no treatment, exercise, exercise and health education as the control, taijiquan has a significant effect on insomnia treatment, and there is no difference in efficacy compared with cognitive behavioral therapy and health education (usual care) alone. Conclusions: The results of the study showed that Taijiquan significantly improved sleep quality in healthy adults and patients with chronic diseases, which suggests that Taijiquan may be considered as an alternative behavioral therapy in the treatment of insomnia. In the future, more high-quality, well-controlled randomized trials are needed to better inform clinical decisions.
ABSTRACT
Background: Disorder of consciousness (DoC) is a clinical condition caused by severe brain damage. Some studies have reported that acupuncture, a traditional Chinese treatment, could facilitate the recovery of the patient's consciousness. The therapeutic effects of acupuncture may be due to its modulation of facilitating cortex (PFC) activity, but it has not been greatly demonstrated. Objectives: We intended to observe the effects of acupuncture on prefrontal cortical activity, explore the potential correlation between cortical activation and the severity of DoC, and analyze the functional brain network connectivity to provide a theoretical basis for its application in clinical practice. Methods: Participants diagnosed with DoC were included in the study. Before the intervention, we assessed the patient's state of consciousness using relevant scales, such as the Glasgow coma scale (GCS) and the coma recovery scale-revised (CRS-R). All patients received acupuncture manipulation with the functional near-infrared spectroscopy (fNIRS) system monitored. Result: A total of 16 subjects participated in our study. We observed that the concentration of oxygenated hemoglobin (HbO) in the PFC was increased during the acupuncture manipulation and declined during the resting state. Then, the connection strength of the left cerebral cortex was generally higher than that of the right. Finally, we observed only a weak difference in hemodynamic responses of PFC between the vegetative state (VS) and minimally conscious state (MCS) groups. However, the difference was not statistically significant. Conclusion: Our results indicated that acupuncture can increase the concentration of HbO in the PFC and strengthen the connection strength of the left cerebral cortex. However, our present study did not find a significant correlation between the cortical hemodynamic response and the severity of DoC.
ABSTRACT
Palladium nanosheets (Pd NSs) are well-investigated photothermal therapy agents, but their catalytic potential for tumor therapy has been underexplored owing to the inactive dominant (111) facets. Herein, lattice tensile strain is introduced by surface reconstruction to activate the inert surface, endowing the strained Pd NSs (SPd NSs) with photodynamic, catalase-like, and peroxidase-like properties. Tensile strain promoting the photodynamic and enzyme-like activities is revealed by density functional theory calculations. Compared with Pd NSs, SPd NSs exhibit lower photothermal effect, but approximately five times higher tumor inhibition rate. This work calls for further study to activate nanomaterials by strain engineering and surface reconstruction for catalytic therapy of tumors.
Subject(s)
Nanostructures , Neoplasms , Catalysis , Humans , Nanostructures/therapeutic use , Neoplasms/therapy , Palladium , PhototherapyABSTRACT
Previous studies have revealed that gypenosides produced from Gynostemma pentaphyllum (Thunb.) Makino are mainly dammarane-type triterpenoid saponins with diverse structures and important biological activities, but the mechanism of diversity for gypenoside biosynthesis is still unclear. In this study, a combination of isobaric tags for relative and absolute quantification (iTRAQ) proteome analysis and RNA sequencing transcriptome analysis was performed to identify the proteins and genes related to gypenoside biosynthesis. A total of 3925 proteins were identified by proteomic sequencing, of which 2537 were quantified. Seventeen cytochrome P450 (CYP) and 11 uridine 5'-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) candidate genes involved in the side chain synthesis and modification of gypenosides were found. Seven putative CYPs (CYP71B19, CYP77A3, CYP86A7, CYP86A8, CYP89A2, CYP90A1, CYP94A1) and five putative UGTs (UGT73B4, UGT76B1, UGT74F2, UGT91C1 and UGT91A1) were selected as candidate structural modifiers of triterpenoid saponins, which were cloned for gene expression analysis. Comprehensive analysis of RNA sequencing and proteome sequencing showed that some CYPs and UGTs were found at both the transcription and translation levels. In this study, an expression analysis of 7 CYPs and 5 UGTs that contributed to gypenoside biosynthesis and distribution in G. pentaphyllum was performed, providing consistent results that will inspire more future research on vital genes/proteins involved in gypenoside biosynthesis.
Subject(s)
Cytochrome P-450 Enzyme System/genetics , Glucuronosyltransferase/genetics , Gynostemma/growth & development , Chromatography, Liquid , Cloning, Molecular , Cytochrome P-450 Enzyme System/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Glucuronosyltransferase/metabolism , Gynostemma/genetics , Gynostemma/metabolism , Plant Extracts/biosynthesis , Plant Proteins/genetics , Plant Proteins/metabolism , Proteomics , Sequence Analysis, RNA , Tandem Mass SpectrometryABSTRACT
OBJECTIVES: This study reviewed and evaluated existing evidence of the efficacy of acupuncture as a clinical treatment for dysphagia after stroke. METHODS: Five English and four Chinese databases were searched from inception to March 2020. All randomized controlled trials (RCTs) incorporating acupuncture or acupuncture combined with other interventions for the treatment of dysphagia after stroke were enrolled. All data were independently assessed and extracted by two authors. The bias risk assessment recommended by the Cochrane Collaboration's tool was used to assess the quality of the selected studies. This meta-analysis was conducted by using RevMan 5.3. Pooled analyses were calculated by the mean difference (MD) and 95% confidence interval (CI). Heterogeneity was assessed by the I 2 test. RESULTS: Thirty-five studies involving 3024 patients were analyzed. The meta-analysis showed that the therapeutic efficacy of acupuncture combined with other interventions was better than that of the control group for the standardized swallowing assessment (SSA) score (MD = -3.78, 95% CI: -4.64 to -2.91, P < 0.00001), Ichiro Fujishima rating scale (IFRS) score (MD = 1.68, 95% CI: 1.16 to 2.20, P < 0.00001), videofluoroscopic swallowing study (VFSS) score (MD = 2.26, 95% CI: 1.77 to 2.74, P < 0.00001), and water swallowing test (WST) score (MD = -1.21, 95% CI: -1.85 to -0.57, P= 0.0002). In studies reporting adverse effects, no serious outcome from an adverse event was confirmed. CONCLUSION: This systematic review indicated that acupuncture could be an effective therapy for treating dysphagia after stroke although stricter evaluation standards and rigorously designed RCTs are needed.
ABSTRACT
Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has shown a great prospect in cancer treatment. However, its therapeutic effect is restricted by the depth of light penetration in tissue and tumor hypoxia environment. Herein, inspired by the specific response of nanozymes to the tumor microenvironment (TME), a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform (denoted as FePc/HNCSs) is constructed using hollow nitrogen-doped carbon nanospheres (HNCSs) and iron phthalocyanine (FePc). FePc/HNCSs simultaneously exhibit peroxidase (POD)- and catalase (CAT)-like activities, which not only can convert endogenous hydrogen peroxide (H2 O2 ) into highly toxic hydroxyl radicals (â¢OH) for catalytic therapy, but also decompose H2 O2 to oxygen (O2 ) to enhance O2 -dependent PDT. In addition, their enzyme-like activities are significantly enhanced under light irradiation. Combining with the excellent photothermal effect, FePc/HNCSs realize a high tumor inhibition rate of 96.3%. This strategy opens a new horizon for exploring a more powerful tumor treatment nanoplatform.
Subject(s)
Neoplasms , Photochemotherapy , Humans , Neoplasms/drug therapy , Phototherapy , Tumor Hypoxia , Tumor MicroenvironmentABSTRACT
Chemo-phototherapy, as a promising cancer combination therapy strategy, has attracted widespread attention. However, the complex tumor microenvironment restricts the penetration depth of chemo-phototherapy agents in the tumor region. Here, biodegradable amphiphilic gelatin (AG) wrapped nanocomposite (PRDCuS@AG) composed of doxorubicin and copper sulfide (CuS)-loaded dendrimer is designed for deep tumor chemo-phototherapy. PR in PRDCuS@AG represents arginine-conjugated polyamidoamine dendrimer. PRDCuS@AG can rapidly biodegrade into PRDCuS by matrix metalloproteinases under near-infrared light irradiation. The resulted PRDCuS harbors dual cell-tissue penetration ability, which can effectively penetrate deep into the tumor tissue. In particular, PRDCuS@AG achieves photoacoustic imaging-guided synergistic chemo-phototherapy with 97% of tumor inhibition rate. Moreover, PRDCuS@AG can further degrade into 3 nm ultrasmall CuS, which can be eliminated from the body after treatment to avoid side effects. This strategy provides an insight that the development of chemo-phototherapy agents with high penetration ability to overcome the limitation of current deep tumor therapy.
Subject(s)
Hyperthermia, Induced , Nanocomposites , Nanoparticles , Neoplasms , Doxorubicin , Humans , Infrared Rays , Neoplasms/therapy , Phototherapy , Tumor MicroenvironmentABSTRACT
Pd nanosheets (Pd NSs) have attracted extensive attention due to their promising application in photothermal therapy. However, their photodynamic properties have rarely been reported. Herein, holey Pd NSs (H-Pd NSs) with intrinsic photodynamic and hypoxia-resistant capacities are fabricated for the first time using an anisotropic oxidative etching strategy, which introduces one-dimensional nanoholes with active (100) facets on the hole walls. Gradual degradation of H-Pd NSs is observed in simulated physiological media due to the oxidative etching. In vitro and in vivo studies indicate that the single-component H-Pd NSs can act as a photothermal/photodynamic agent for imaging-guided hypoxic tumor therapy, with a high tumor inhibition rate of 99.7%. This work provides ideas for introducing active facets in metallic pore walls, broadening the application of Pd NSs and the design of biodegradable noble metal nanotheranostic agents for cancer therapy.
Subject(s)
Antineoplastic Agents/therapeutic use , Nanopores , Nanostructures/therapeutic use , Neoplasms/drug therapy , Palladium/therapeutic use , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Female , Infrared Rays , Mice, Inbred BALB C , Nanostructures/chemistry , Nanostructures/radiation effects , Palladium/chemistry , Palladium/radiation effects , PhotochemotherapyABSTRACT
Two-dimensional (2D) nanomaterials are currently explored as novel photothermal agents because of their ultrathin structure, high specific surface area, and unique optoelectronic properties. In addition to single photothermal therapy (PTT), 2D nanomaterials have demonstrated significant potential in PTT-based synergistic therapies. In this Minireview, we summarize the recent progress in 2D nanomaterials for enhanced photothermal cancer therapy over the last five years. Their unique optical properties, typical synthesis methods, and surface modification are also covered. Emphasis is placed on their PTT and PTT-synergized chemotherapy, photodynamic therapy, and immunotherapy. The major challenges of 2D photothermal agents are addressed and the promising prospects are also presented.
Subject(s)
Nanomedicine/methods , Nanostructures/chemistry , Nanostructures/therapeutic use , Phototherapy/methods , Animals , Humans , Neoplasms/therapyABSTRACT
Carbon nanomaterials have flourished for cancer therapy for decades. However, their practical applications on clinical bases still pose a challenge to address the dilemma of metabolism in vivo. In this study, an attempt is made to design a degradable carbon-silica nanocomposite (CSN) with immunoadjuvant property, which could undergo an enzyme-free degradation process into small particles (â¼5 nm) and facilitate its clinical application. CSN harbors photothermal and photodynamic properties and as an immunoadjuvant would help to generate tumor-associated antigens and mature dendritic cells (DCs). Potent antitumor effects have been achieved in both 4T1 and patient-derived xenograft tumor models with tumor inhibition efficiencies of 93.2% and 92.5%, respectively. We believe that this strategy will benefit the possible clinical translation and carbon-silica-nanomaterial-based cancer therapy.
Subject(s)
Antigens, Neoplasm/immunology , Breast Neoplasms/drug therapy , Photochemotherapy , Photosensitizing Agents/pharmacology , Phototherapy , Adjuvants, Immunologic , Animals , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Carbon/chemistry , Carbon/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Dendritic Cells/immunology , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/immunology , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Nanocomposites/chemistry , Optical Imaging , Particle Size , Photosensitizing Agents/chemistry , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , Surface PropertiesABSTRACT
BACKGROUND: Functional electrical stimulation (FES) plus body weight-supported treadmill training (BWSTT) provide effective gait training for poststroke patients with abnormal gait. These features promote a successful active motor relearning of ambulation in stroke survivors. AIM: This is a retrospective study to assess the effect of FES plus BWSTT for gait rehabilitation in patients poststroke. DESIGN: A retrospective case-matched study. SETTING: Participants were recruited from a rehabilitation department in an acute university-affiliated hospital POPULATION: Ninety patients poststroke from Yue Bei People's Hospital underwent BWSTT (A: control group) were compared to an equal number of cross-matched patients who received FES plus BWSTT (B: FES plus BWSTT group). METHODS: While B group received FES for 45 minutes plus BSWTT for 30 minutes in the program, group A received time-matched BWSTT alone. The walking speed, step length, step cadence, Fugl-Meyer Lower-Limb Scale (LL-FMA), composite spasticity scale (CSS), 10-Meter Walk Test (10MWT), Tinetti Balance Test (TBT) and nerve physiology testing were collected before and after intervention. RESULTS: One hundred and eighty patients with poststroke abnormal gait were chosen. There were significant differences in walking speed, step length, step cadence, LL-FMA, CSS, TBT, and 10MWT between baseline and postintervention (P<0.05). There were significant differences in walking speed, step length, step cadence, LL-FMA, CSS, TBT, and 10MWT between two groups at the end of the eighth week (P<0.05), but not at baseline (P>0.05). In comparison with group A, the peak of somatosensory evoked potential (SEP) and motor evoked potential (MEP) amplitude increased, the latency was shortened, and the conduction velocity of sensory nerve (SCV) and motor nerve (MCV) was significantly increased in the group B (P<0.05). No adverse events occurred during the study. CONCLUSIONS: This study suggests that FES plus BWSTT could be more effective than BWSTT alone in the improvement of gait, balance, spasticity, and function of the lower limb in patients poststroke. CLINICAL REHABILITATION IMPACT: Introduce effective rehabilitation strategies for poststroke patients with abnormal gait.
Subject(s)
Electric Stimulation Therapy/methods , Gait Disorders, Neurologic/physiopathology , Gait Disorders, Neurologic/rehabilitation , Stroke Rehabilitation/methods , Aged , Combined Modality Therapy , Disability Evaluation , Female , Humans , Male , Middle Aged , Retrospective Studies , Stroke/physiopathology , Walk TestABSTRACT
Although near-infrared (NIR)-light-mediated photothermal thrombolysis has been investigated to overcome the bleeding risk of clinical clot-busting agents, the secondary embolism of post-phototherapy fragments (>10 µm) for small vessels should not be ignored in this process. In this study, dual-modality photothermal/photodynamic thrombolysis is explored using targeting nanoagents with an emphasis on improving biosafety as well as ameliorating the thrombolytic effect. The nanoagents can actively target glycoprotein IIb/IIIa receptors on thrombus to initiate site-specific thrombolysis by hyperthermia and reactive oxygen species under NIR laser irradiation. In comparison to single photothermal thrombolysis, an 87.9% higher re-establishment rate of dual-modality photothermal/photodynamic thrombolysis by one-time treatment is achieved in a lower limb thrombosis model. The dual-modality thrombolysis can also avoid re-embolization after breaking fibrin into tiny fragments. All the results show that this strategy is a safe and validated protocol for thrombolysis, which fits the clinical translational trend of nanomedicine.
ABSTRACT
Enzymes have been used to direct the conversion of prodrugs in cancer therapy. However, non-specific distribution of endogenous enzymes seriously hinders their bioapplications. Herein, we developed a near-infrared-triggered locoregional chemo-photothermal therapy based on the exogenous enzyme delivery and remolded tumor mivroenvironment. The catalytic efficiency of enzymes was enhanced by the hyperthermia, and the therapeutic efficacy of photothermal therapy (PTT) was improved owing to the inhibition of heat shock protein 90 by chemotherapeutics. The locoregional chemo-phototherapy achieved a one-time successful cure in 4T1 tumor-bearing mice model. Thus, a mutually reinforcing feedback loop between PTT and chemotherapy can be initiated by the irradiation, which holds a promising future in cancer therapy.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/therapy , Glycoside Hydrolases/metabolism , Hyperthermia, Induced , Photochemotherapy/methods , Phototherapy/methods , Prodrugs/pharmacology , Animals , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Proliferation , Combined Modality Therapy , Drug Delivery Systems , Drug Liberation , Female , Glucosinolates/metabolism , Gold/chemistry , Humans , Infrared Rays , Isothiocyanates/metabolism , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Mice , Prodrugs/chemistry , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Gold complexes can serve as efficient photothermal converters for cancer therapy, but their non-biodegradability hinders clinical bioapplications. Although enormous effort has been devoted, the conventionally adopted synthetic methods of biodegradation are characterized by high cost and complicated procedures, which delay the process of further clinical translation of gold complexes. Here, we report a multifunctional poly(amino acid)-gold-magnetic complex with self-degradation properties for synergistic chemo-photothermal therapy via simple and green chemistry methods. Nanoparticles of â¼3 nm in the biodegradation product were observed in simulated body fluid in 4 days. The biodegradability mainly benefits from the weakened internal electrostatic interaction of the poly(amino acid) by the ions in simulated body fluid. It is demonstrated that the poly(amino acid)-gold-magnetic complex has great cellular endocytosis by taking advantage of the guanidine group in arginine and possesses multimodal imaging and efficient tumor ablation (94%). This study reports a possibility for gold-magnetic complexes composed of poly(amino acid) to serve as a biodegradable nanotherapeutic for clinical applications.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Biocompatible Materials/chemistry , Doxorubicin/pharmacology , Gold/chemistry , Magnetite Nanoparticles/chemistry , Mammary Neoplasms, Animal/therapy , Phototherapy , Polyglutamic Acid/chemistry , Animals , Antibiotics, Antineoplastic/chemistry , Biocompatible Materials/metabolism , Cell Line, Tumor , Doxorubicin/chemistry , Endocytosis/drug effects , Female , Gold/metabolism , Mammary Neoplasms, Animal/diagnostic imaging , Mammary Neoplasms, Animal/metabolism , Mice , Mice, Inbred BALB C , Polyglutamic Acid/metabolism , Static ElectricityABSTRACT
Although nanoparticle-based photothermal therapy (PTT) has been intensively investigated recently, its comparative efficiency with any clinical cancer treatments has been rarely explored. Herein for the first time we report a systematic comparative study of clinical iodine-125 (125 I) interstitial brachytherapy (IBT-125-I) and interventional PTT (IPTT) in an orthotopic xenograft model of human pancreatic cancer. IPTT, based on the nanoparticles composing of anti-urokinase plasminogen activator receptor (uPAR) antibody, polyethylene glycol (PEG), and indocyanine green (ICG) modified gold nanoshells (hereinafter uIGNs), is directly applied to local pancreatic tumor deep in the abdomen. In comparison to IBT-125-I, a 25% higher median survival rate of IPTT with complete ablation by one-time intervention has been achieved. The IPTT could also inhibit pancreatic tumor metastasis which can be harnessed for effective cancer immunotherapy. All results show that this IPTT is a safe and radical treatment for eradicating tumor cells, and may benefit future clinical pancreatic cancer patients.
Subject(s)
Pancreatic Neoplasms , Cell Line, Tumor , Gold , Humans , Indocyanine Green , Nanoshells , Phototherapy , Polyethylene GlycolsABSTRACT
Recently, photothermal therapy (PTT) has become viewed as an ideal auxiliary therapeutic treatment for cancers. However, the development of safe, convenient, and highly effective photothermal agents remains a great challenge. In this study, we prepared single-walled carbon nanotubes (SWNTs) for PTT against breast tumors under the guidance of infrared fluorescent cyanines. Tumors were accurately located using near-infrared imaging (NIR) and then exposed to laser irradiation. Both the in vivo and in vitro results showed that the SWNTs have high stability and low cytotoxicity. Introducing polyethylene glycol into our nanoparticles increased the blood-circulation time. Our in vivo results further showed that Cy5.5-conjugated SWNTs mediated PTT, resulting in efficient tumor suppression in mice under the guidance of near-infrared imaging. Due to the small amount of absorption at 808-nm, Cy5.5 increased the efficiency of PTT. Breast tumors significantly shrunk after irradiation under the 808-nm near-infrared laser. The treated mice developed scabs, but otherwise recovered after 15 days, and their physical conditions restored gradually. These data indicate that our unique photothermal-responsive SWNT-Cy5.5-based theranostic agent can serve as a promising candidate for PTT.