ABSTRACT
@#Gas chromatography-mass spectrometry (GC-MS) method was established for trace analysis of the potential genotoxic impurity chlorocyclohexane in trihexyphenidyl hydrochloride bulk drug, utilizing an RXI-5SIL MS column at isothermal temperature of 60 °C for the entire 6-minute run time.The inlet temperature was 180 °C and a split ratio of 10∶1 was used with the injection volume of 1.0 μL.The selective ion monitoring mode was set at m/z 82 for chlorocyclohexane with a detector voltage of 0.3 kV and an ion source temperature of 240 °C.The method was verified with respect to specificity, limit of detection (LOD), limit of quantitation (LOQ), accuracy, precision and robustness.Good linear correlation was achieved with coefficient r of 0.999 9 in the concentration range of 59.72-493 ng/mL.The intra- and inter-day precision was satisfactory (RSD ≤ 5.0%) and robust (RSD ≤ 1.65%).The proposed method in this study can be adequately adopted as a tool for quality assurance of trihexyphenidyl hydrochloride in routine test of potential genotoxic impurity.
ABSTRACT
Chimeric antigen receptor (CAR) T-cell therapy is the most active field in immuno-oncology and brings substantial benefit to patients with B cell malignancies. However, the complex procedure for CAR T-cell generation hampers its widespread applications. Here, we describe a novel approach in which human CAR T cells can be generated within the host upon injecting an Adeno-associated virus (AAV) vector carrying the CAR gene, which we call AAV delivering CAR gene therapy (ACG). Upon single infusion into a humanized NOD.Cg-Prkdcscid Il2rgem26/Nju tumor mouse model of human T-cell leukemia, AAV generates sufficient numbers of potent in vivo CAR cells, resulting in tumor regression; these in vivo-generated CAR cells produce antitumor immunological characteristics. This instantaneous generation of in vivo CAR T cells may bypass the need for patient lymphodepletion, as well as the ß processes of traditional CAR T-cell production, which may make CAR therapy simpler and less expensive. It may allow the development of intricate, individualized treatments in the form of on-demand and diverse therapies.
Subject(s)
Dependovirus , Genetic Therapy , Genetic Vectors , Leukemia, T-Cell , Receptors, Chimeric Antigen , Transduction, Genetic , Animals , HEK293 Cells , Humans , Jurkat Cells , Leukemia, T-Cell/genetics , Leukemia, T-Cell/immunology , Leukemia, T-Cell/therapy , Mice , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/immunology , Xenograft Model Antitumor AssaysABSTRACT
@#A Mn-clusters-porphyrin metal-organic framework nanosheet(nMn-MOF)was synthesized by coordination chelation to enhance photodynamic therapy. The nanosheet was characterized by dynamic light scattering, transmission electron microscopy and X-ray photoelectron spectroscopy. Oxygen sensor and ICG were used to investigate the production of oxygen and the singlet oxygen(1O2)generation. The cytotoxicity of the nanosheet against tumor cells were detected by CCK-8 assay, and the anti-hypoxia and oxygen-generation ability of nanosheets were investigated by fluorescence staining assay. The results indicated that this nanosheet could catalyze the intracellular H2O2 into O2, which overcame the tumor hypoxia. Furthermore, the generated oxygen was converted to cytotoxic 1O2 under the near infrared light irradiation, thereby enhancing photodynamic therapy.
ABSTRACT
@#Abstract:Photodynamic therapy(PDT)is a minimal invasive therapy that have been clinically approved for the cancer treatment with selective cell toxicity. When activated by appropriate wavelength of light, photosensitizers transfer the absorbed photon energy to the surrounding molecular oxygen to generate reactive oxygen species, which result in cell death, vessel damage and immune activation of tumor site. This paper summarize the main challenges and recent solutions for PDT application, such as the low tissue penetration of light, toxicity induced by nonspecific accumulation of skin and poor PDT effect of hypoxia tumor.
