| Nanoparticle-mediated chemotherapy can achieve precise treatment of tumors,but the clinical application of nanocarrier chemotherapy faces a series of challenges such as high efficiency selectivity,release controllability,and biosecurity.The responsive design and surface modification of nanocarriers according to the specificity of the tumor microenvironment can solve the biosecurity problem of the vector after entering the blood circulation,and the different functional molecules of the surface modification can achieve multiple responses and treatment of the carrier.Based on the challenges faced by nanodrug carriers,we have designed a series of stimulus-responsive nanodrug vectors for efficient tumor treatment.(1)In order to improve the drug treatment efficiency and biosafety,a p H-responsive degradable nanoparticle DOX@PDA/MSN-CMCS-FA was designed.MSN)as the matrix material,the acylation reaction linked carboxymethyl chitosan(CMCS)on the surface of the silica spheres,and finally the prepared folate active ester(FA-NHS)was anchored on the surface.In acidic environment(p H=5.0,6.5)and neutral environment(p H=7.2),the drug release rates are 40%,22%and 16%,and the size changes between 350-360 nm at 7 d,2 W/m~2 After near-infrared light irradiation,the half-lethal concentration of nanomedicines to cells was reduced to 14.95μg/m L.Nanomedicines possess p H-responsive drug release properties and photothermal synergy.(2)The ROS/UV light dual-responsive targeted controlled release system DOX@MSN-TK-CD/GAP was designed to enhance the difference in stimuli response,and mesoporous silica with uniform particle size was synthesized by the oil-water two-phase method(MSN),the reactive oxygen species-responsive thioketal(TK)group was attached to the surface of aminated silica,and thenβ-CD-NH2 was attached to block the mesopores,and finally the liver cancer-targeting polymer was prepared through the main The guest interaction is attached to the nanoparticle surface.The size of the material DOX@MSN-TK-CD/GAP is about 220 nm.Through the drug release experiment,when ROS and UV light stimulation exist at the same time,the release is about 12%more than that without stimulation.Cell experiments show that the carrier is more conducive to Hep G2 endocytosis,The IC50 of DOX on cells was 5.521μg/m L in the UV light group,9.46μg/m L in the absence of light,and 14.67μg/m L in the non-stimulated response group.This proves that the carrier can control the release of the drug by UV light and reactive oxygen species.(3)Enhanced intracellular active oxygen in the second chapter and drug load stability,using anenexate to prepare a near-infrared light-responsive nano-drug polymer Zn PC@P(PEG-CMA-TKGEM)The thirytanocarbone bond provides an active oxygen response,phthalocyanine zinc(Zn Pc)provides an active oxygen generating agent and a cell imaging developer to achieve near-infrared photocontrolled drug release.The micelle is spherical,and the size is about 134 nm is a positive distribution,and the release rate of 48 hours under NIR irradiation is 3 times higher than that of the control group,and the intracellular experiment has observed the extension of the illumination time,and the cells have increased green fluorescence.The production of active oxygen proves.The cell survival rate of the latching group in the cell experiment was about 17%,and the survival rate of the photographic cells was>80%.It is proved that the nano-drug carrier has the characteristics of exogenous light stimulation treatment. |
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