#5420 A MODULAR INTRACELLULAR HIERARCHICAL-RESPONSIVE NANOCARRIER ENABLES DUAL TARGETING FOR HIGH THERAPEUTIC EFFICACY IN KIDNEY DISEASE

Abstract Background and Aims Single-loaded nanocarrier that can improve targeting capability drug toxicity compared with free drugs demonstrates a promising strategy for disease treatment. Due to the heterogeneity of injured cells during progression, dose-induced resistance, instability nanocarriers in blood circulation, it is challenging achieve dual different cell subsets as well reducing dosage but obtaining efficient In addition, developing complex time-consuming process; there desire develop universal various diseases, especially ones. Here, we have successfully designed modular capable co-delivery drugs. Meanwhile, effective was reduced one-tenth single-loaded nanocarriers. Method The dual-loaded drug-targeting nanoparticles consist four main modules, including chemical material, an antibody, two First, constructed mesoscale spherical nanoparticle particle size 400 nm from PLGA wrapped A inside it. Next, foot cell-specific antibody Nephrin used target material modified on surface by ph-sensitive short peptide. Finally, B coupled obtain final dual-targeting dual-drug nanoparticles. were injected into mice via tail vein evaluate their organs immune system drug. We explored mechanisms organ imaging, Immunofluorescence, other experimental methods. mice, established model acute kidney injury, puromycin aminonucleoside nephropathy (PAN), ccRCC compare protective effects concentrations. Results Dual loaded demonstrated ability glomeruli tubules. treating encapsulated rapamycin dexamethasone acetate; nephropathy, changed captopril; treatment cancer models, gefitinib glutathione chosen targeted antitumor For lesions treated significantly combinations. observed reduction tubular injury model, recovery process podocytes foci renal model. These results show drug-loaded nanomaterials excellent cope situations. Conclusion delivery flexibly adapt diseases changing size, antibodies,