AIM: The objective of the present study is to prepare and characterize nutlin-3a loaded polymeric @entity10124 nanoparticles (NPs) surface functionalized with @entity69 ligand, to deliver the encapsulated drug in a targeted manner to its site of action and to evaluate the efficacy of the nanoformulation in terms of its cellular uptake, cell cytotoxicity, cell cycle arrest, apoptosis and activation of @entity876 pathway at molecular level in MCF-7 @entity0 cell line. METHOD: Nutlin-3a loaded @entity10124 NPs were prepared following the single oil-in-water emulsion method. Physicochemical characterization of the formulation included size and surface charge measurement, transmission electron microscopy characterization, study of surface morphology using scanning electron microscopy, Fourier-transform infrared spectral analysis and in vitro release kinetics studies. Furthermore, targeting ability of the conjugated system was assessed by cellular uptake and cell cytotoxicity studies in an in vitro cell model. Molecular basis of nutlin-3a-mediated @entity876 activation pathway was investigated by western blot analysis. Inhibition of cell cycle progression and apoptosis was evaluated by flow cytometry. RESULTS: Physiochemical characterization of the formulations revealed that nutlin-3a was efficiently encapsulated in the nanoparticulate system, reaching an encapsulation efficiency of approximately 80% with size of approximately 220 nm and negative zeta potential of approximately -10.4 mV. Higher cellular uptake efficiency of the conjugated system proved the effectiveness of targeted therapy. IC(50) values, as determined by @entity34962 assay, showed superior antiproliferative activity of @entity69 -conjugated NPs over unconjugated NPs and native nutlin-3a, owing to enhanced cellular uptake by @entity5 cells. At the molecular level the conjugated system showed enhanced activation of @entity876 pathway in comparison to native drug as evident from western blot analysis. Augmented cell cycle arrest and apoptosis was exhibited by the conjugated system. Thus, our results suggest that @entity69 -conjugated nutlin-3a loaded NPs could be a potential drug carrier system for targeted delivery of potent anticancer drug nutlin-3a for @entity0 therapy.

Targeted nutlin-3a loaded nanoparticles inhibiting @entity876 -MDM2 interaction: novel strategy for XXXX therapy.

@entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity69 :: ('7018', 'Gene') :: ['transferrin'] @entity34962 :: ('CHEBI:53238', 'Chemical') :: ['3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium'] @entity876 :: ('7157', 'Gene') :: ['p53'] @entity10124 :: ('CHEBI:53493', 'Chemical') :: ['poly(lactide-co-glycolide)']
@entity0 :: (MESH:D001943,Disease) :: ['breast cancer']
