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The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death (ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators. Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.
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Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NH
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In recent years, mesoporous silica nanoparticles (MSNs) have been widely used in the construction of various intelligent drug delivery systems due to their unique and excellent properties. The stimuli-responsive drug delivery system based on mesoporous silica nanoparticles can effectively load anticancer drugs and target them to tumor cells, and then responsively release anticancer drugs under the action of specific stimulation signals. The method of specifically delivering anticancer drugs to target sites not only can greatly improvethe drug efficacy, but also effectively reduce the side effects of anticancer drugs on normal tissues and organs. Thereby the advantages of anticancer drugs in tumor therapy are improved. In this paper, the applications and developments of stimuliresponsive mesoporous silica nano drug delivery systems in tumor therapy were summarized.
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Malignant tumors are the second most important cause of death after cardiovascular and cerebrovascular diseases. Chemotherapeutic drugs for tumor treatment have strong toxic side effects. The common solution is to use nanoparticle as a carrier that can deliver drugs to tumor issues so as to kill the tumor cells. However, most of the current drug-carriers have a serious drug loss before reaching the tumor area, which makes the difficult control of drug release. Multi-stimulus responsive nano-carrier systems can overcome these drawbacks and make drug release controllable. pH/redox dual sensitive nano-carrier systems are currently hot research direction. In this paper, the research progress of pH/redox dual sensitive nano-carrier systems in recent years was reviewed in order to provide reference for relative researches.
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In recent years,the incidence of malignant tumors continually increased with the trend of younger age in onset age,which pose a serious threat to human health.At present,there are a variety of clinical anti-tumor treatments.However,a single treatment usually cannot achieve the best therapeutic effect.As a result,the combination therapy is often used in clinical practice.Combination therapy not only can enhance the therapeutic effect and reduce the toxic side effects of drugs,but also can alleviate the pain of patients.Chemotherapy is a commonly used clinical treatment for tumors.However,it can lead to greater side-effects,and cause irreversible damage to normal cells while killing the tumor cells.Photodynamic therapy uses the specific wavelengths of light to excite and activate the photosensitizer enriched in the tumor local.As a result,the tumor cells are killed directly or indirectly by photodynamic reactions with the participation of internal oxygen.Tumorassociated antigen will appear following the chemotherapy or photodynamic therapy.The immune system will stimulate the body to produce specific anti-tumor immune response after identifying the tumor-associated antigens.The combination treatment of chemotherapy and photodynamic therapy combined with immunotherapy not only can effectively improve the treatment effect of chemotherapy drugs and reduce drug side effects,inhibit tumor metastasis,but also can induce the production long-term anti-tumor immune response,so as to maximize the treatment effect.In this paper,the progress of the researches on chemotherapy,photodynamic therapy and immunotherapy in recent years were summarized.
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In recent years,the incidence of malignant tumors continually increased with the trend of younger age in onset age,which pose a serious threat to human health.At present,there are a variety of clinical anti-tumor treatments.However,a single treatment usually cannot achieve the best therapeutic effect.As a result,the combination therapy is often used in clinical practice.Combination therapy not only can enhance the therapeutic effect and reduce the toxic side effects of drugs,but also can alleviate the pain of patients.Chemotherapy is a commonly used clinical treatment for tumors.However,it can lead to greater side-effects,and cause irreversible damage to normal cells while killing the tumor cells.Photodynamic therapy uses the specific wavelengths of light to excite and activate the photosensitizer enriched in the tumor local.As a result,the tumor cells are killed directly or indirectly by photodynamic reactions with the participation of internal oxygen.Tumorassociated antigen will appear following the chemotherapy or photodynamic therapy.The immune system will stimulate the body to produce specific anti-tumor immune response after identifying the tumor-associated antigens.The combination treatment of chemotherapy and photodynamic therapy combined with immunotherapy not only can effectively improve the treatment effect of chemotherapy drugs and reduce drug side effects,inhibit tumor metastasis,but also can induce the production long-term anti-tumor immune response,so as to maximize the treatment effect.In this paper,the progress of the researches on chemotherapy,photodynamic therapy and immunotherapy in recent years were summarized.
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Breast cancer is one of the most common cancers.The clinical treatment of breast cancer has made great progress,but the inherent or acquired drug resistance,tumor migration and tumor infiltration,which lead to poor treatment efficiency and eventually death,are still the urgent problems to be solved.As with the occurrence and development of common tumors,the abnormal proliferation,migration and infiltration of breast tumor cells and muhidrug resistance (MDR) are closely related to the abnormal expression of specific genes in the cell.At present,many studies have found that the occurrence and development of tumor is closely related to the abnormal expression of microRNA.Therefore,in order to better understand the molecular mechanism of the occurrence and development of breast cancer,it is necessary to study the function of microRNA in breast tumor cells.In this paper,the application of microRNA in the treatment of breast cancer was reviewed,striving for providing effective ideas for the future selection of new strategies to control the development of tumors.
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Objective To prepare stable aqueous dispersions of chitosan/multi-walled carbon nanotubes (CS/MWCNTs) composites,and observe the effects of CS/MWCNTs on the growth of human umbilical vein endothelial cells (HUVEC).Methods CS/MWCNTs composites were prepared by electrostatic interactions between negatively charged MWCNTs and positively charged low-molecular-weight CS.The prepared CS/MWCNTs were characterized by transmission electron microscopy and Zetasizer nano-analyser.The cellular uptake of the fluorescently labeled CS/MWCNTs was observed by laser confocal microscopy after incubating with HUVEC for 24 h at different concentrations.In vitro cytotoxicity and cellular reactive oxygen were also detected.Results When the mass ratio of low-molecular-weight CS to MWCNTs was equal or greater than 10∶1,the CS/MWCNTs can be stabilized in solution.Cellular uptake experiments showed that the CS/MWCNTs could enter into the cells and locate mainly in the cytoplasm.Cytotoxicity study showed that the CS/MWCNTs composites was less toxic than MWCNTs alone at high concentration (10 and 20 μg/ml).However,there was no significant differencein the level of cellular reactive oxygen between the two groups (P＜0.05).Conclusions CS/MWCNTs composites showed low cytotoxicity and high stability,which would be a promising carrier for drug delivery.
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Objective To analyze the effect of dexmedetomidine hydrochloride injection on patients with craniocerebral disease who has no artificial airway in the process of bronchoalveolar lavage treatment.Methods Forty-six patients (age 17-28,average age 56.6±9.2,26 men and 20 women) with craniocerebral disease who has no artificial airway were selected,and were treated by bronchoalveolar lavage for lung infection.The patients were randomly divided into two groups,control and test group.The control group (n=23) received midazolam for sedative and the test group (n=23) received dexmedetomidine hydrochloride for sedative while they were in the process of bronchoalveolar lavage treatment.Heart rate,mean arterial pressure and blood oxygen saturation of fingers collected from patients before and during the process of bronchoalveolar lavage were compared.Results In the process of bronchoalveolar lavage treatment,the minimum blood oxygen saturation of finger artery from the control group was lower than that from the test group,the fastest heart rate from the control group was greater than that from the test group,and the lowest mean arterial pressure from the control group was lower than that from the test group (P＜0.05).In two groups,heart rate in the process of bronchoalveolar lavage treatment was faster than that from before the treatment,while both mean arterial pressure and blood oxygen saturation of finger artery were decreased (P＜0.05).Conclusions Continuous intravenous pumping of dexmedetomidine hydrochloride on patients with craniocerebral disease who has no artificial airway during the process of bronchoalveolar lavage treatment is effective and safe,and it has less inhibitory effect on respiratory function and blood pressure.
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Objective To detect the size distribution and Zeta potential of LHRH-MPG△NLS/CDK-siRNA nanoparticles,to observe the effect of different solvents on the nanoparticle size,and to investigate the inhibitory effect of nanoparticles on HepG2 cell growth.Methods LHRH-MPG △NLS and CDK2-siRNA were mixed by continuous stirring to form nanoparticles at different N/P ratios (10/1,20/1 and 40/1).The size distribution and Zeta potential of LHRH-MPG△NLS/CDK2-siRNA nanoparticles were detected by dynamic light scattering,and the stability of the nanoparticles in normal saline,10％ glucose and pure water was discussed.Finally,the inhibitory effect of the nanoparticles on HepG2 cells was determined by CCK8 kit.Results The mean size of the nanoparticles was within 200 nm,and the Zeta potentials were (70±5) mV (N/P=10/1),(120±5) mV (N/P=20/1) and (130±5) mV (N/P=40/1),respectively.The size of the nanoparticles in normal saline was significantly increased,which demonstrated that strong electrolytes had a great impact on the nanoparticles size.When nanoparticle concentration was 200 nmol/L,LHRH-MPG△NLS/CDK2-siRNA nanoparticles (N/P=10/1) showed significantly inhibitory effect on HepG2 cell growth.Conclusions The mean size of the LHRH-MPG△NLS/CDK2-siRNA nanoparticles was within 200 nm,which was ideal for cellular uptake.The Zeta potential of nanoparticles revealed that nanoparticles could be stable in aqueous solution,while strong electrolytes would affect nanoparticle size.When nanoparticle concentration was 200 nmol/L,LHRH-MPG△NLS/CDK2-siRNA nanoparticles (N/P=10/1) showed significantly inhibitory effect on HepG2 cell growth.
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Objective To investigate the cell compatibility of polystyrene(PS) plate chemically modified with RGD peptides.Methods PS surfaces were carboxylated by permanganate oxidation in diluted sulfuric acid,and carboxyls were activated with water-soluble carbodiimide to graft with gelatin,collagen and RGD peptides.IR,X-ray photo-electronic spectroscopy (XPS) and dynamic contact angle were used to characterize the surface modification of PS surface.Results XPS results confirmed the existence of nitrogen element from protein molecules and the covalently binding of proteins to PS surfaces.Dynamic contact angle measurement indicated hydrophilicity of PS surfaces was improved obviously after grafting modification.The cell culture results showed that the cell adhesion and proliferation was better on modified surfaces than the initial.Conclusion The cell compatibility of PS surface was great improved after modification with RGD peptides,which would provide a potential strategy to improve the culture of purified endothelial progenitor cells isolated by immunomagnetic beads.
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ObjectiveTo investigate the cytotoxicity and gene transfection mediated by NMPCS/DNA nanoparticles.MethodsN-methylene phosphonic chitosan (NMPCS) was synthesized using one-step reaction under homogeneous conditions.The NMPCS/DNA nanoparticles were prepared using complex coacervation method.The cytotoxicity of NMPCS alone and its complexes with plasmid DNA were determined by MTT assay on HeLa cells.The gene transfection mediated by NMPCS/DNA nanoparticles were investigated using pGL3control vector as reporter gene.ResultsThe MTT results suggested that the NMPCS and NMPCS/DNA complexes showed significantly lower cytotoxicity than PEI and PEI/DNA complexes,respectively.The gene transfection mediated by NMPCS/DNA nanoparticles were greatly improved compared with unmodified chitosan.ConclusionNMPCS would demonstrate great potential as a novel,safe,efficient non-viral vector for gene delivery.
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Objective To investigate the effects of different thickness of cell culture dishes on fluorescent image with confocal microscope.Methods The fluorescent staining experiments of live cells and fixed cells were used to determine the differences among three dishes with different thickness coverslips of 0.085～0.13 mm,0.13～0.16 mm and 0.16～0.19 mm,while the cell appearance,fluorescence lightness and mean of fluorescence intensity were studied with confocal microscope.Results Demonstrated by the results of cytoskeleton staining experiments,the dish with 0.13～0.16 mm thickness coverslip was the best choice for confocal microscope,the dish with 0.16～0.19 mm thickness coverslip was the second one,the dish with 0.16～0.19 mmthickness coverslip was the last one.ConclusionThe dish with 0.13～0.16 mm thickness coverslip is the best choice for confocal microscope.On this type of dish,the cytoskeleton is unfolding and clear after staining.The intensity of fluorescence is the strongest,and the imaging effect is the best.
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ObjectiveConjugation of fluorescent dye onto plasmid DNA was investigated in order to monitor delivery process of plasmid DNA.MethodsPlasmid was activated with bromine,stored for different timeintervals at 4 ℃ or room temperature,and subsequently coupled with 1,10-diaminodecane to prepare aminemodified plasmid DNA.Amine-modified plasmid was then reacted with isothiocyanate (FITC) for fluorescent labeling,and the labeling ratio was calculated after purification.The effect of storage conditions (time/temperature) of bromine-actived plasmid (BP) on fluorescent labeling efficacy was estimated,and the cell transfection efficiency of fluorescent plasmid-lipofectamine complex was observed.The fluorescent plasmid delivered by lipofectamine 2000 in A10 cells was observed by laser scanning confocal microscope (LSCM) and flow cytometry.ResultsThe experimental data showed that prolonged storage time of bromine-activated DNA had a negative effect on the labeling ratio,and lower storage temperature had a positive effect on the labeling ratio.It also demonstrated that FITC modification had no effect on the transfection efficiency of plasmid-lipofectamine complex as compared with that of unlabeled plasmid-lipofectamine complex,and FITC modified plasmid had enough fluorescent intensity to monitor cell uptake with flow cytometer and sub-cellular distribution with LSCM.ConclusionA facile method for conjugating fluorescent dye onto plasmid was established in the study,and could be utilized to trace the plasmid delivery for investigating the transfection mechanism.
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ObjectiveTo isolate and identify endothelial progenitor cells (EPCs) from human umbilical cord,and to study the cell proliferation and gene transfection of green fluorescent protein plasmid in vitro.MethodsEPCs were isolated from human umbilical cord in enzyme digestion method.The biological characteristics of EPCs were identified by flow cytometry and laser confocal microscope.The enhanced green fluorescent protein (EGFP) gene transfection mediated by EPCs was investigated using Lipofectamine 2000 as transfection reagent.ResultsEndothelial progenitor cells isolated from umbilical cord formed typical endothelial cell colony 9 days later.These cellsdisplayed an improved positive expression of CD133 and kinase insert domain receptor (KDR).The endotheliallineage characteristics of expanded cells were confirmed by fluorescein isothiocyanate (FITC)-UEA-1 binding and DiI-ac-LDL uptake assay with the aid of laser confocal microscope.The transfection results demonstrated high expression of EGFP taking EPCs as host cell.ConclusionEndothelial progenitor cells isolated from umbilical cord can be propagated and induced to differentiate into endothelial cells in the appropriate culture conditions.EPCs demonstrated to be an ideal carrier for gene and cell therapy.
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Objective To investigate the impact of chitosan and alkylated chitosan DNA nanoparticles on the function of human naive CD4+T cells.Methods The secretion of cytokines (IL-4 and TNF-γ) was observed after the co-incubation of human naive CD4+T cells with nanoparticles 12 h,24 h and 48 h,respectively.ResultsNone of the nanoparticles induced the production of cytokines ( IL-4 and TNF-γ ).Conclusion Chitosan and alkylated chitosan DNA nanoparticles will not induce the differentiation of human naive CD4+ T cells into T1 or T2 and may be considered as a safe gene carrier.
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The biosafety of gene delivery vectors has received much more attention in recent years. In this article, the biosafety of non-viral gene delivery vectors was mainly discussed. Recent developments in researches on toxicity, nano-effect, blood compatibility and immune response of non-viral gene delivery vectors were reviewed.