摘要
Multidrug resistance(MDR) and targeted therapies remain as vital challenges in tumor chemotherapy.Nanoparticles provide promising application for cancer theranostics as for their excellent advantages of tumor-targeted cytotoxicity and imaging capability.In present study,we developed N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride(HTCC)/alginate encapsulated Fe_3O_4 magnetic nanoparticles(HTCC-MNPs) and applied it into MDR gastric cancer both in vivo and in vitro.HTCC-MNPs were fabricated using ALG,Fe_3O_4 and HTCC in ionic gelation method.The size and physical characteristics of nanoparticles were detected by dynamic light scattering,transmission electron microscopy(TEM) and zeta potential analysis.HTCC-MNPs exhibited excellent water solubility and biocompatibility and significantly reduced cell viability in drug-resistant cancer cell line SGC7901/ADR cells but not in normal gastric cells(P < 0.05).LC3 analysis demonstrated the involvement of autophagy in HTCC-MNPs cytotoxicity.Additionally,apoptosis was verified by DNA content assay.HTCC-MNPs led to mitochondrial membrane potential loss,decreased ATP production and excessive reactive oxygen species(ROS) generation as compared with control group(P < 0.05).Magnetic resonance imaging showed the enrichment of HTCC-MNPs in tumor-bearing mice.In vivo.Bioluminensence imaging and tumor volume measurement revealed that HTCC-MNPs markedly inhibited in vivo tumor growth(P < 0.05).In conclusion,HTCC-MNPs significantly inhibited MDR gastric tumor growth and decreased tumor volume via the induction of cellular autophagy and apoptosis,which was attributed to mitochondrial dysfunction and excessive ROS accumulation.
Multidrug resistance(MDR) and targeted therapies remain as vital challenges in tumor chemotherapy.Nanoparticles provide promising application for cancer theranostics as for their excellent advantages of tumor-targeted cytotoxicity and imaging capability.In present study,we developed N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride(HTCC)/alginate encapsulated Fe_3O_4 magnetic nanoparticles(HTCC-MNPs) and applied it into MDR gastric cancer both in vivo and in vitro.HTCC-MNPs were fabricated using ALG,Fe_3O_4 and HTCC in ionic gelation method.The size and physical characteristics of nanoparticles were detected by dynamic light scattering,transmission electron microscopy(TEM) and zeta potential analysis.HTCC-MNPs exhibited excellent water solubility and biocompatibility and significantly reduced cell viability in drug-resistant cancer cell line SGC7901/ADR cells but not in normal gastric cells(P < 0.05).LC3 analysis demonstrated the involvement of autophagy in HTCC-MNPs cytotoxicity.Additionally,apoptosis was verified by DNA content assay.HTCC-MNPs led to mitochondrial membrane potential loss,decreased ATP production and excessive reactive oxygen species(ROS) generation as compared with control group(P < 0.05).Magnetic resonance imaging showed the enrichment of HTCC-MNPs in tumor-bearing mice.In vivo.Bioluminensence imaging and tumor volume measurement revealed that HTCC-MNPs markedly inhibited in vivo tumor growth(P < 0.05).In conclusion,HTCC-MNPs significantly inhibited MDR gastric tumor growth and decreased tumor volume via the induction of cellular autophagy and apoptosis,which was attributed to mitochondrial dysfunction and excessive ROS accumulation.
引文