Nanoconjugation of receptor ligands represent a nanoparticle-based strategy to impact and modulate cellular signaling but the underlying nanoparticle-cell interactions and regulation mechanisms remain insufficiently understood. In the case of the epidermal growth factor (EGF), nanoconjugation has been demonstrated to shift the signaling from growth and proliferation to apoptosis, but the role of the nanoparticle in the enhancement of apoptosis remains to be defined. Here, we characterize the apoptotic efficacy of nanoconjugated EGF as function of nanoparicle size, aspect ratios, and EGF surface loading and provide experimental evidence for the size- and morphology-dependences of the apoptotic effect. A characterization of the cellular processes that induce apoptosis reveals that nanoconjugated EGF increases cytoplasmic reactive oxygen species (ROS) levels and reduces intracellular glutathione (GSH) levels. The perturbation of the intracellular redox homeostasis is an important checkpoint in the induction of apoptosis. A potential mechanism for the EGFR-dependent change in the intracellular milieu as response to nanoconjugated EGF is proposed. The observation that ligands for cancer biomarkers, such as EGFR, can be reprogrammed through nanoconjugation to induce apoptosis provides new opportunities for overcoming apoptosis enhancement in cancer with benign ligands. <br/>

Reprogramming growth factor signaling through nanoconjugation

255th National Meeting (2018)

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