Development of novel functional silica nanoparticles has drawing great attention in the field of fluorescent sensing as they provide advantages in term of versatile functionalization, high stability, and good biocompatibility. In the present work, a dual-fluorophore-functionalized mesoporous silica nanoparticle was designed and fabricated, where two silanized fluorophores, NAA and RB-2, were chemically bound to the nanoparticle surface. A series of measurements including TEM, BET, FT-IR, TGA and XPS were carried out to characterize the morphology variation and verify the surface functionalization. Fluorescence measurements revealed that the fluorescent nanoparticle displayed typical naphthalene and rhodamine emission bands, where the naphthalene units exhibited weak fluorescence emission due to the modification of 2,4-dinitrobenzenesulfonyl group (DNBS). The reaction with biothiols led to departure of DNBS group and thereby recovered the fluorescence of naphthalene unit. The presence of different biothiols resulted in different extents of fluorescence changes of naphthalene and rhodamine. Moreover, the dual-fluorophore functionalized nanoparticle at different concentration showed different responses to the same biothiol and was used as sensing element to construct a two-element sensor array. By collecting the four signals, the mini sensor array could provide distinct recognition pattern and can realize fingerprint discrimination of the four biothiols (H2S, Cys, Hcy, GSH) in aqueous solution and human serum.

The RAP12 peptide derived from miniaturization of receptor-associated protein (RAP) holds binding affinity with low-density lipoprotein receptor-related protein-1 (LRP1). However, RAP12 exhibited weak a-helical segments when taken out of the stabilizing protein context. Considering that the alpha-helix is a common structural motif of the peptide to mediate ligand-receptor interactions, we utilized the peptide stapling technique to generate RAP12 with all-hydrocarbon tethers, named stapled RAP12 (ST-RAP12). This optimized ST-RAP12 was verified to obtain an increased a-helical content, binding affinity with LRP1 and serum stability compared to RAP12. In addition, ST-RAP12 exhibited enhanced cellular internalization of bEnd.3 cell, U87 glioma cells and HUVEC. Furthermore, the ability of ST-RAP12 to overcome in vitro BBB/BBTB was also potentiated. Next, ST-RAP12 peptide was further applied to modify polymeric materials to construct ST-RAP12-micelles. It is verified that the ST-RAP12-micelles effectively penetrated BBB/BBTB and targeted glioma in vitro/vivo, and immunofluorescence studies demonstrated its targeting ability to tumor angiogenesis and LRP1. Moreover, ST-RAP12-micelles efficiently delivered paclitaxel (PTX) to glioma, prolonged the survival time of glioma-bearing mice, inhibited tumor angiogenesis and induced glioma apoptosis, which displayed obvious anti-glioma efficacy. Overall, ST-RAP12 is anticipated to be a widely used LRP1-targeted peptide and could be translated as a multifunctional ligand for glioma-targeted drug delivery.