Polyvinylpyrrolidone functionalization induces deformable structure of graphene oxide nanosheets for lung-targeting delivery

Abstract Nanomaterials (NMs) as lung-targeted drug delivery vehicles have attracted great attentions. Recent studies indicated that elastic or deformable property of NMs could play a vital role in biomedical applications. Herein, polyvinylpyrrolidone (PVP) functionalized graphene oxide (GO-PVP) via a facile one-pot method and PEGylated GO (GO-PEG) nanosheets (NSs) were synthesized at room temperature. By using rare earth elemental labeling method, we quantitatively revealed that GO-PVP NSs were targeting retention in the lung that after 4 h intravenous injection, the lung/liver and lung/spleen ratios in GO-PVP treated mice were about 230-fold and 30-fold higher of those in GO-PEG treated mice, respectively, especially a considerable amount was retained in the lower respiratory tract including pulmonary interstitium and alveolar region as fibril-like shapes. The florescence imaging and in situ confocal Raman microscopy combining with laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) elemental imaging analysis further confirmed that a more amount of GO-PVP than GO-PEG retention in the pulmonary interstitium. Utilizing atomic force microscopy PeakForce quantitative nanomechanical mapping technique, the nanomechanical property investigation shows that GO-PVP NSs are softer, more adhesive and deformable than GO-PEG NSs. Further, the molecular dynamics simulations illustrate that GO-PVP has deformable structure due to the hydrogen-bond interaction at basal plane between PVP and GO that cause GO-PVP surface roughness and to possess low solvent accessible surface area (SASA), comparatively, the GO-PEG owns relatively firm structure and higher SASA. This study indicates that the well dispersion property and deformable structure of GO-PVP in the lung contribute to its filtration of the endothelial/epithelial barrier and retention in the interstitium and alveolar region. Importantly, the study inspires us to design elastic or deformable NMs in response to the lung disease especially those have occurred in the lower respiratory tract.