Camouflaging multifunctional nanoparticles with bacterial outer membrane for augmented chemodynamic/photothermal/starvation/chemo multimodal synergistic therapy of orthotopic glioblastoma

Innovative therapeutic strategy and effective drug delivery are significant challenges in current glioblastoma multiforme (GBM) therapy. The development of efficient combination therapy based on chemodynamic therapy (CDT) has attracted widespread attention in recent years. Herein, a lipopolysaccharide-free bacterial outer membrane vesicles (dOMV) camouflaged biomimetic nanoreactor was constructed for quadruple synergistic therapy of orthotopic GBM. Benefiting from the immune escaping property and blood–brain barrier (BBB) penetration capacity of dOMV, nanoreactors can target cancer cells and accumulate in the tumor site. Firstly, for quadruple synergistic therapy, Glucose oxidase (GOx) can rapidly consume intratumoral glucose to generate H 2 O 2 and gluconic acid for starvation therapy. Secondly, the abundant H 2 O 2 produced by the enzyme-catalyzed reaction can continuously supply Cu 9 S 8 -mediated Fenton-like reaction to enhance CDT. Meanwhile, tumor hypoxic microenvironment exacerbated by GOx-induced oxygen depletion activated prodrug AQ4N for chemotherapy. Finally, the second near-infrared (NIR-II) absorbed Cu 9 S 8 increased the temperature in local tumor site upon NIR-II laser irradiation, which can achieve photothermal-enhanced CDT, elevate GOx activity, and accelerate drug release. In vitro and in vivo results demonstrated that the camouflaging multifunctional nanoparticles with bacterial outer membrane ( [email protected] 9 S 8 @dOMV) was a promising multifunctional therapeutic nanomedicine platform for highly efficient treatment of GBM, which may be extended to as a treatment option for clinical cancer theranostics.