RESUMO
There is an outstanding need for targeted therapies for triple-negative breast cancer (TNBC), an aggressive breast cancer subtype. Since TNBC's rapid growth and metastasis are driven by hyperactive Wnt signaling, suppressing the key-pathway mediator ß-catenin through RNA interference may improve patient outcomes. However, small interfering ribonucleic acid (siRNA) molecules require a carrier to elicit targeted gene silencing. Here, we show that 4T1 cancer cell membrane wrapped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) can deliver siRNA into TNBC cells, silence ß-catenin expression, and reduce the cells' tumorigenic qualities. Compared to unwrapped and nontargeted NPs, the cancer cell membrane wrapped nanoparticles (CCNPs) exhibit dramatically improved uptake by TNBC cells versus breast epithelial cells and greater gene silencing at mRNA and protein levels. Congruently, ß-catenin siRNA-loaded CCNPs significantly activate senescence in 2D cultured TNBC cells and reduce proliferation in 3D spheroids. This work advances the development of nucleic acid carriers for targeted RNA interference therapy.
Assuntos
Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Interferência de RNA , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , RNA Interferente Pequeno/genética , Nanopartículas/uso terapêuticoRESUMO
A model calculation was used to assess whether the G-DRG version 1.0 sufficiently represents integrated internal psychosomatic treatment of patients with psychosomatic disorders in relation to diagnosis and resource consumption. The DRGs of the Major Diagnostic Category "Mental Diseases" of the German DRG calculation sample 1.0 (diagnoses, procedures, cost weights) were analyzed. In a division of psychosomatic medicine within a general internal department, proceeds regarding 241 patients treated between 01 Jan and 31 Dec 2002, calculated according to the G-DRG version 1.0, were compared to the costs accrued. The G-DRG version 1.0 includes 7 DRGs of psychosomatic disorders in internal medicine (excluding disorders due to substance abuse). Assuming a base rate of euro 2,900, the total proceeds of the G-DRG Version 1.0 exceeded the costs (+ euro 57,971 /year).