RESUMO
This study leverages nanotechnology by encapsulating indocyanine green (ICG) and paclitaxel (Tax) using zeolitic imidazolate frameworks-8 (ZIF-8) as a scaffold. This study aims to investigate the chemo-photothermal therapeutic potential of ZIF-8@ICG@Tax nanoparticles (NPs) in the treatment of non-small cell lung cancer (NSCLC). An "all-in-one" theranostic ZIF-8@ICG@Tax NPs was conducted by self-assembly based on electrostatic interaction. First, the photothermal effect, stability, pH responsiveness, drug release, and blood compatibility of ZIF-8@ICG@Tax were evaluated through in vitro testing. Furthermore, the hepatic and renal toxicity of ZIF-8@ICG@Tax were assessed through in vivo testing. Additionally, the anticancer effects of these nanoparticles were investigated both in vitro and in vivo. Uniform and stable chemo-photothermal ZIF-8@ICG@Tax NPs had been successfully synthesized and had outstanding drug releasing capacities. Moreover, ZIF-8@ICG@Tax NPs showed remarkable responsiveness dependent both on pH in the tumor microenvironment and NIR irradiation, allowing for targeted drug delivery and controlled drug release. NIR irradiation can enhance the tumor cell response to ZIF-8@ICG@Tax uptake, thereby promoting the anti-tumor growth in vitro and in vivo. ZIF-8@ICG@Tax and NIR irradiation have demonstrated remarkable synergistic anti-tumor growth properties compared to their individual components. This novel theranostic chemo-photothermal NPs hold great potential as a viable treatment option for NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Liberação Controlada de Fármacos , Verde de Indocianina , Neoplasias Pulmonares , Nanopartículas , Paclitaxel , Nanomedicina Teranóstica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Verde de Indocianina/química , Humanos , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Concentração de Íons de Hidrogênio , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Paclitaxel/química , Paclitaxel/farmacologia , Camundongos , Zeolitas/química , Raios Infravermelhos , Fototerapia/métodos , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Células A549 , Estruturas Metalorgânicas/química , Camundongos Nus , Sistemas de Liberação de Medicamentos , ImidazóisRESUMO
OBJECTIVE: To study the effect of chronic poisoning of ketamine on brain cell apoptosis in adult mouse under different duration and doses. METHODS: The mouse model of chronic poisoning of ketamine was established on adult mouse by tail vein injection of ketamine twice every week with different doses (4, 10, 20 and 30 mg/kg). The mice were sacrificed after continuous injection of ketamine of 1, 2, 4, 8 and 12 weeks. The qualitative assessment of apoptosis was made by transmission electron microscope and the quantitative assessment was made by Caspase-3 immumofluorescence staining method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to estimate the time point of apoptosis. All the experimental results were statistically analyzed. RESULTS: The neuron apoptosis was observed in hippocampus and corpus striatum by transmission electron microscope one week after administration, and continued for eight weeks. High level of Caspase-3 expression was observed one week after administration, but with a low level expression after 4 weeks. The number of TUNEL positive cells obviously increased one week after administration and maintained in a high number at 4 weeks. CONCLUSION: Ketamine by tail vein injection could induce neuron apoptosis in adult mouse.