Glioblastoma (GBM) treatment faces a significant challenge due to the blood-brain barrier (BBB) restricting therapeutic delivery. In this study, we found that inactivated and attenuated meningitis bacteria (e.g., Escherichia coli K1) intracellularly loaded with nanoagents could safely and effectively bypass the BBB even when injected intravenously into mice at a dose of ~10⁷ CFU since the vehicles preserved the bacteria’s structure and chemotaxis while removing their pathogenicity. We demonstrated bacteria could internalize glucose polymer, indocyanine green and stimulator of interferon genes (STING) agonists (e.g., SR717)-modified silica nanoparticles through the bacteria-specific ATP-binding cassette sugar transporter pathway. As a result, the developed system could deliver approximately five times more nanoagents to the brain than free nanoagents. Upon 808-nm irradiation, the indocyanine green induced photothermal effects that destroyed the bacteria, releasing the SR717, which triggered adaptive antitumor immunity, and the bacterial remnants further induced innate antitumor immunity. Our findings demonstrate that this inactivated nanobacteria system effectively treats GBM in mice, suggesting potential for broader applications in central nervous system disorders.

Traditional photothermal agents of indocyanine green (ICG) have poor stability, short circulation time, and poor brain permeability due to the blood–brain barrier (BBB), greatly impairing their therapeutic efficacy in glioblastoma (GBM). Herein, we develop a novel kind of SiNPs-based nanoprobes to bypass the BBB for photothermal therapy of GBM. Typically, the SiNPs-based nanoprobes are composed of the particle itself, the BBB-targeting ligand of glucosamine (G), and the therapeutic agent of ICG. We demonstrate that the as-synthesized nanoprobes could cross the BBB through glucose transporter-1 (GLUT1)-mediated transcytosis, followed by accumulation at GBM tissues in mice. Compared with free ICG, G-ICG-SiNPs show stronger stability (for example, the fluorescence intensity of G-ICG-SiNPs loaded with the same dose of ICG decays by 34.6% after 25 days of storage, while the fluorescence intensity of ICG decays by 99.5% under the same conditions). Furthermore, the blood circulation time of G-ICG-SiNPs increases by about 17.3-fold compared with their ICG counterparts. After injection of the therapeutic agents into the GBM-bearing mice, GBM-surface temperature rises to 45.3 °C in G-ICG-SiNPs group after 5-min 808 nm irradiation but climbs only to 36.1 °C in equivalent ICG group under the identical conditions, indicating the superior photothermal effects of G-ICG-SiNPsin vivo.

The production of bimetallic nanoparticles with ultrasmall sizes is the constant pursuit in chemistry and materials science because of their promising applications in catalysis, electronics and sensing. Here we report ambient-temperature preparation of bimetallic NPs with tunable size and composition using microfluidic-controlled co-reduction of two metal precursors on silicon surface. Instead of free diffusion of metal ions in bulk system, microfluidic flow could well control the local ions concentration, thus leading to homogenous and controllable reduction rate among different nucleation sites. By controlling precursor concentration, flow rate and reaction time, we rationally design a series of bimetallic NPs including Ag-Cu, Ag-Pd, Cu-Pt, Cu-Pd and Pt-Pd NPs with ultrasmall sizes (~ 3.0 nm), tight size distributions (relative standard deviation (RSD) < 21%), clean surface, and homogenous elemental compositions among particles (standard deviation (SD) of weight ratios < 3.5%). This approach provides a facile, green and scalable method toward the synthesis of diverse bimetallic NPs with excellent activity.