Photostable and Biocompatible Fluorescent Silicon Nanoparticles-Based Theranostic Probes for Simultaneous Imaging and Treatment of Ocular Neovascularization.

Ocular neovascularization can result in devastating diseases that lead to marked vision impairment and eventual visual loss. In clinical implementation, neovascular eye diseases are first diagnosed by fluorescein angiography and then treated by multiple intravitreal injections, which nevertheless involves vision-threatening complications, as well as lack of real-time monitoring disease progression and timely assessment of therapeutic outcomes. To address this critical issue, we herein present a kind of theranostic agents made of peptide-functionalized silicon nanoparticles (SiNPs), suitable for simultaneous ocular neovascularization imaging and therapy. Typically, in addition to negligible toxicity and high specific binding ability to human retinal microvascular endothelial cells tube formation, the cyclo-(Arg-Gly-Asp-d-Tyr-Cys) ( c-(RGDyC))-conjugated SiNPs (SiNPs-RGD) features efficacious antiangiogenic ability in wound healing migration, transwell migration, transwell invasion, and tube formation assays. Taking advantage of these unique merits, we further employ the SiNPs-RGD for labeling angiogenic blood vessels and neovascularization suppression, demonstrating obvious inhibition of new blood vessels formation in mouse corneas. These results suggest the SiNPs-RGD as a novel class of high-quality theranostic probes is suitable for simultaneous diagnosis and treatment in ocular neovascular diseases.

Biocompatible protamine sulfate@silicon nanoparticle-based gene nanocarriers featuring strong and stable fluorescence.

The development of biocompatible and fluorescent gene carriers is of particular importance in the gene-delivery field. Taking advantage of the unique optical properties (e.g., strong and robust fluorescence) of silicon nanoparticles (SiNPs), as well as the excellent biocompatibility of silicon and protamine sulfate (PS, approved by the U.S. Food and Drug Administration (FDA) for clinical use), we herein present a type of PS-modified SiNP (PS@SiNP)-based gene carrier. Plasmid DNA (pDNA) with negative charges can be effectively bound onto the surface of the as-prepared fluorescent PS@SiNP-based gene carriers via electrostatic interactions. In particular, such resultant gene carriers possess stable and high fluorescence (photoluminescent quantum yield (PLQY): ∼25%). In addition, the PS@SiNP-based gene carriers show minimal toxic effects on normal mitochondrial metabolic activity (e.g., human retinal pigment epithelial (ARPE-19) cells preserve ∼90% of their cell viability after a 48 h incubation with the resultant carriers). Based on tracking the strong and stable fluorescence signals of SiNPs, the dynamic behavior of the PS@SiNP-based gene carriers in live cells (e.g., clathrin-mediated endocytosis, lysosomal escape, pDNA release, etc.) is investigated in a long-term manner, providing valuable information for understanding the intracellular behavior of gene vectors and designing high-efficacy gene carriers.