Cancer immunotherapy aims at stimulating the immune system to react against cancer stealth capabilities. It consists of repeatedly injecting small doses of a tumor-associated molecule one wants the immune system to recognize, until a consistent immune response directed against the tumor cells is observed.
We have applied the theory of optimal control to the problem of finding the optimal schedule of injections of an immunotherapeutic agent against cancer. The method employed works for a general ODE system and can be applied to find the optimal protocol in a variety of clinical problems where the kinetics of the drug or treatment and its influence on the normal physiologic functions have been described by a mathematical model.
We show that the choice of the cost function has dramatic effects on the kind of solution the optimization algorithm is able to find. This provides evidence that a careful ODE model and optimization schema must be designed by mathematicians and clinicians using their proper different perspectives. 相似文献
The work described the synthesis and evaluation of PEI-g-comb-PEG-transferrin as a potential system for gene therapy in vitro. The MW of PEG was 10KDa, and PEI was 2KDa. Its structure was identified by NMR, FT-IR and TGA spectroscopy. MTT assay found that at concentration up to 4000 n mol/L of the polymer, cell viability was over 85%. The bio-character of polymer/DNA complex was characterized by agarose gel electrophoresis, ethidium bromide exclusion and zeta-potential assay. The polymer could retardate DNA at N/P ratio 3.0-3.5 (mol/mol). The particle size of the polymer/DNA complex was less than 300 nm. Transfection efficiency of the complex was studied in COS7 and NT2 cell lines. 相似文献
Anion starch nanoparticle (StNP) with a diameter of 50 nm was prepared in water-in-oil microemulsion, with soluble starch
as raw materials and POCl3 as crosslinking agent. PLL-StNP was prepared by linking poly-L-lysine (PLL) on the surface of StNP. At the same time, the
size of PLL-StNP and its stability in aqueous solution were checked by AFM. The analysis of plasmid DNA binding, DNase I enzymatic
degradation, toxicity and transfection were done. We discovered that PLL-StNP may be used as non-virus nanoparticle gene carrier.
And we developed the method of preparing PLL-StNP gene carrier and used it in cell transfection. As non-virus gene carrier,
PLL-StNP has some advantages, such as large load of DNA, high transfection efficiency, low cell toxicity and biodegradability. 相似文献
An arginine‐leucine block copolypeptide (R60L20) is synthesized, which is capable of forming vesicles with controllable sizes, able to transport hydrophilic cargo across the cell membrane, and exhibit relatively low cytotoxicity. The R60L20 vesicles also possess the ability to deliver DNA into mammalian cells for transfection. Although the transfection efficiency is lower than that of the commercially available transfection agent Lipofectamine 2000, the R60L20 vesicles are able to achieve transfection with significantly lower cytotoxicity and immunogenicity. This behavior is potentially due to its stronger interaction with DNA which subsequently provides better protection against anionic heparin.
A series of degradable branched PDMAEMA copolymers were investigated with the linear PDMAEMA counterpart as gene‐delivery vectors. The branched PDMAEMA copolymers were synthesized by controlled radical cross‐linking copolymerization based on the “vinyl oligomer combination” approach. Efficient degradation properties were observed for all of the copolymers. The degree of branching was found to have a big impact on performance in transfection when tested on different cell types. The product with the highest degree of branching and highest degree of functionality had a superior transfection profile in terms of both transfection capability and the preservation of cell viability. These branched PDMAEMA copolymers show high potential for gene‐delivery applications through a combination of the simplicity of their synthesis, their low toxicity, and their high performance. 相似文献
Chitosan (CS) is expected to be an ideal gene carrier for its high biosafety. In this work, CS with low molecular weight were prepared through the γ-ray radiation on the acetic acid solution of CS. The CS chains were scissioned under the γ-ray radiation, and the molecular weight (MW) of CS decreased with the absorbed dose. When the absorbed dose was above 30 kGy, the molecular weight of CS decreased about an order of magnitude. The γ-ray-radiation-scissioned CS can e ectively bind with plasmid (pEGFP) through complex coacervation method, forming pEGFP/ γ-ray-radiation-scissioned CS complex particles with a size of 200-300 nm. The complex particles have good stability and little cytotoxicity. The in uitro gene transfection efficiencies of the pEGFP/ γ-ray-radiation-scissioned CS complex particles were investigated by fluorescence microscope and flow cytometry. The results showed that the gene vectors using γ-ray-radiation-scissioned CS as the carrier will possess better gene transfection efficiency than those using natural high-MW CS as the carrier. The higher the absorbed dose, the smaller the MW of CS and the better transfection efficiency of the corresponding gene vector. This work provides a green and simple method on the preparation of CS-based gene vectors with high efficiency and biosafety. 相似文献
探讨12C6+ 离子束辐射对用带有绿色荧光蛋白基因的缺陷性腺病毒(AdCMV GFP)转染小鼠黑色素瘤细胞(B16细胞系)的影响。 采用不同剂量的12C6+ 重离子束辐射经AdCMV GFP 转染的B16细胞, 利用流式细胞仪检测腺病毒的转染率。 结果表明, 12C6+重离子束辐射能提高腺病毒对B16细胞的转染率, 且具有量效关系。 此外, 先转染后辐射法比起先辐射后转染法能更显著地提高转染率。The effect of 12C6+ beam irradiation on AdCMV GFP (a replication deficient recombinant adenoviral vector containing CMV promoter and green fluorescent protein) gene transfection efficiency for murine melanoma cell B16 has been investigated. B16 cells infected with AdCMV GFP were irradiated by different doses of 12C6+ beam. The transfection efficiency was assessed by flow cytometry (FCM). Results show that 12C6+ beam irradiation can improve tansfection efficiency of AdCMV GFP on murine melanoma cell B16 in a dose dependent manner. In addition, the tansfection efficiency in pre tranfection plus irradiation group is higher than that in pre irradiation plus tranfection group at the same dose irradiation dose. 相似文献
A novel approach was developed to introduce biological materials into cells for gene transfection and gene therapy applications. The method is based on the technique of electrospraying bio-materials into cells. A prototype apparatus was constructed for a feasibility study. The features of the gene transfector include: (1) A dual-capillary assembly to spray suspensions of biological materials. The outer capillary provided sheathing liquid that controlled the charge level on individual particles without altering the properties of suspensions. (2) An air–CO2 gas mixture was used for suppressing possible corona discharge and kept the same gas composition as those in incubators. (3) The designed chamber enabled the spray to operate at reduced pressure for increasing sprayed particle velocity. In the feasibility study, both suspensions of plasmid and plasmid-coated gold particles were used. The plasmid used was the commercially available Enhanced Green Fluorescent Protein gene. COS-1 cells were used as the target and the liquid media was evacuated immediately prior to the spraying process. Electrospraying was conducted at ambient pressure and the duration was no more than 2 min. After the spray transfection, the media was immediately replaced and the cell samples were returned to the incubator for 36 h. Transgene expression was detected by cellular fluorescence. This technology promises to have great potential for gene transfection and therapy studies. 相似文献