Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma.

摘要: The establishment of more effective treatments that can circumvent chemoresistance in Multiple Myeloma (MM) is a priority. Although bortezomib (BTZ) one the most potent proteasome inhibitors available, still possesses limitations related to dose limiting side effects. Several strategies have been developed improve delivery chemotherapies MM by targeting different moieties expressed on cells nanoparticle systems (NPs), which failed mainly due their heterogeneous expression these cells. Our goal was test CD38 targeted chitosan NPs as novel moiety for potency and efficacy BTZ reduce effects healthy tissue. We showed preferential release tumor-microenvironment, specific binding cells, an improved drug cellular uptake through diffusion from surface endocytosed NPs, translated enhanced inhibition robust cytotoxic effect when administered anti-CD38 NPs. Furthermore, specifically delivered therapeutic agents improving reducing vivo. low toxicity profile allowing enhancement proteasome-inhibitory activity specificity endocytosis-mediated representing promising therapy MM.