Encapsulation in LbL-NPs improves efficacy and targeted delivery of CDDP in BBB-GBM. (A) GBM spheroid size in BBB-GBM model following treatment with free CDDP, CDDP encapsulated in bare NPs (Bare CDDP NP), or CDDP encapsulated in AP2 NPs (AP2 CDDP NP), compared to untreated devices. Points represent mean ± SD of n = 6 devices. (B) Representative fluorescent micrographs quantified in A. (Scale bars: 200 µm.) (C) Change in MFI of NP signal in GBM tumors in the BBB-GBM device over time, following treatment with fluorescently tagged bare- or AP2-CDDP NPs. Points represent n = 1 device. (D) MFI of Sytox signal per area (normalized by DAPI) in the three ROI locations considered in BBB-GBM devices after treatment with free CDDP, bare CDDP NPs, or AP2 CDDP NPs and compared to control devices without treatment. Points represent n = 1 device. (E) Representative fluorescent micrographs quantified in D. (Scale bar: 500 µm.) (F) Heatmap of cell death gene-expression levels in two ROIs of the devices (inside the GBM tumor and far from the tumor), as quantified by qRT-PCR. Bars represent mean ± SD. ns, not significant. *P < 0.05; ****P < 0.0001. Statistical analyses are described in Materials and Methods. AU, arbitrary units.