Hollow mesoporous silica nanoparticles for tumor vasculature targeting and PET image-guided drug delivery

Aim: Development of multifunctional and well-dispersed hollow mesoporous silica nanoparticles (HMSNs) for tumor vasculature targeted drug delivery and PET imaging. Materials & methods: Amine functionalized HMSNs (150-250 nm) were conjugated with a macrocyclic chelator, (S)-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triaceticacid (NOTA), PEGylated and loaded with antiangiogenesis drug, Sunitinib. Cyclo(Arg-Gly-Asp-D-Tyr-Lys) (cRGDyK) peptide was attached to the nanoconjugate and radiolabeled with Cu-64 for PET imaging. Results: Cu-64-NOTA-HMSN-PEG-cRGDyK exhibited integrin-specific uptake both in vitro and in vivo. PET results indicated approximately 8% ID/g uptake of targeted nanoconjugates in U87MG tumors, which correlated well with ex vivo and histological analyses. Enhanced tumor-targeted delivery of sunitinib was also observed. Conclusion: We successfully developed tumor vasculature targeted HMSNs for PET imaging and image-guided drug delivery.