Optimization of tyrosine kinase inhibitor-loaded gold nanoparticles for stimuli-triggered antileukemic drug release

Abstract

Abstract Tyrosine kinase inhibitor (TKI) therapy is gaining attraction in cancer therapeutics due to the ubiquity of kinases in cell survival and differentiation. Great progress was made in the past years for identifying tyrosine kinases that can function as valuable molecular targets and for the entrapment of their corresponding inhibitors in delivery compounds for triggered release. Herein we present a class of drug-delivery nanocompounds that can serve as theranostic agents against blood cancers. By loading the TKI Midostaurin onto polymer (Pluronic and Polyvinylpyrrolidone)-gold nanoparticles we fabricated nanocompounds with tunable functionalities, particularly the targeting of the FMS-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia. We optimised the nanocompounds formulation with loading efficiencies in the 84–94% range by studying the MDS loading and controlled release behavior when conjugated onto GNPs functionalized with polymers that, in specific conditions, can have stimuli responsive properties. The drug release dinamics were investigated and the therapeutic efficiency of MDS-loaded particles was confirmed with toxicities that depend on specific dosage ranges. The targetability and imaging capability were demonstrated via dark field (DF) microscopy. No effect was observable on FLT3 negative cells or for unloaded particles. Beyond druggability, we can track this type of nanocarriers inside biological structures, which might contribute to the facilitation of the personalized drug dosage administration, critical for attaining a maximal therapeutic effect.