Polyethylene glycol (PEG) has been successfully used for improving circulation time of several nanomaterials but prolonging the circulation of porous silicon nanoparticles (PSi NPs) has remained challenging. Here, we report a site specific radiolabeling of dual-PEGylated thermally oxidized porous silicon (DPEG-TOPSi) NPs and investigation of influence of the PEGylation on blood circulation time of TOPSi NPs. Trans-cyclooctene conjugated DPEG-TOPSi NPs were radiolabeled through a click reaction with [111In]In-DOTA-PEG4-tetrazine (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and the particle behavior was evaluated in vivo in Balb/c mice bearing 4T1 murine breast cancer allografts. The dual-PEGylation significantly prolonged circulation of [111In]In-DPEG-TOPSi particles when compared to non-PEGylated control particles, yielding 10.8 ± 1.7% of the injected activity/g in blood at 15 min for [111In]In-DPEG-TOPSi NPs. The improved circulation time will be beneficial for the accumulation of targeted DPEG-TOPSi to tumors.

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Targeted delivery of diagnostics and therapeutics offers essential advantages over nontargeted systemic delivery. These include the reduction of toxicity, the ability to reach sites beyond biological barriers, and the delivery of higher cargo concentrations to diseased sites. Virus-like particles (VLPs) can efficiently be used for targeted delivery purposes. VLPs are derived from the coat proteins of viral capsids. They are self-assembled, biodegradable, and homogeneously distributed. In this study, hepatitis E virus (HEV) VLP derivatives, hepatitis E virus nanoparticles (HEVNPs), were radiolabeled with gallium-68, and consequently, the biodistribution of the labeled [ 68 Ga]Ga-DOTA-HEVNPs was studied in mice. The results indicated that [ 68 Ga]Ga-DOTA-HEVNPs can be considered as promising theranostic nanocarriers, especially for hepatocyte-targeting therapies.

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