Co-delivery of DOX and PDTC by pH-sensitive nanoparticles to overcome multidrug resistance in breast cancer.

Co-delivery of DOX and PDTC by pH-sensitive nanoparticles to overcome multidrug resistance in breast cancer. Colloids Surf B Biointerfaces. 2019 May 20;181:185-197 Authors: Cheng X, Li D, Sun M, He L, Zheng Y, Wang X, Tang R Abstract Chemotherapeutic drugs have a series of limitations in the conventional clinical treatments, mainly including serious adverse effects and multidrug resistance (MDR). Herein, we developed a pH-sensitive polymeric nanoparticle with using poly(ortho ester urethanes) copolymers for co-delivering doxorubicin (DOX) and pyrrolidinedithiocarbamate (PDTC) to settle these problems. Dual-drug-loaded nanoparticles were nano-sized (˜220 nm) with the spherical morphology and excellent physiological stability. Both drugs both could be quickly released in the mild acidic conditions due to the cleavage of ortho ester bonds. Monolayer cultured cells (2D) and multicellular spheroids (3D) experiments proved that PDTC could reverse multidrug resistance (MDR), improve intracellular drugs accumulation and enhance tumor penetration by down-regulating the expression of P-gp, then resulting in higher DOX-induced cytotoxicity and apoptosis in MCF-7 and MCF-7/ADR cells. Besides, in vivo experiments further demonstrated that co-encapsulated nanoparticles had higher DOX accumulation and superiorer tumor growth inhibition (TGI 82.9%) than free drugs or single-drug-loaded nanoparticles on MCF-7/ADR bearing-mice. Accordingly, the pH-...
Source: Colloids and Surfaces - Category: Biotechnology Authors: Tags: Colloids Surf B Biointerfaces Source Type: research