Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy

Abstract

Bacteria can bypass the blood-brain barrier (BBB), suggesting the possibility of employment of bacteria for combating central nervous system diseases. Herein, we develop a bacteria-based drug delivery system for glioblastoma (GBM) photothermal immunotherapy. The system, which we name as ‘Trojan bacteria’, consists of bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles. In an orthotopic GBM mouse model, we demonstrate that the intravenously injected bacteria bypass the BBB, targeting and penetrating GBM tissues. Upon 808 nm-laser irradiation, the photothermal effects produced by ICG allow the destruction of bacterial cells and the adjacent tumour cells. Furthermore, the bacterial debris as well as the tumour-associated antigens promote antitumor immune responses that prolong the survival of GBM-bearing mice. Moreover, we demonstrate the residual bacteria are effectively eliminated from the body, supporting the potential therapeutic use of this system.

Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma

“…The orthotopic GBM models using GL261 and G422 were established as previously reported with some modification 16,71 . In brief, 2 × 10 5 GL261, GL261-luc, GL261-GFP, or G422 cells in 5 μL PBS were injected into right corpus striatum of C57BL/6 or Kunming mice by using a stereotaxic apparatus.…”

In vivo bioluminescence imaging of natural bacteria via ATP-binding cassette sugar transporter

“…Among these subunits, LamB is a typical outer membrane diffusion porin, and MalE can recognize α (1-4)-glucosidically linked GP molecules [41][42][43][44][45][46][47] . By leveraging this uptake mechanism, small-size (e.g., ~ 5 nm) GP-modi ed nanoparticles including silicon nanoparticles, gold nanoparticles and carbon dots recently have been demonstrated to be selectively and robustly internalized into bacterial cells [48][49][50] . Analogously, diverse bacteria eat their camou aged 'foods', i.e., GP-Si-BPs and GP-Si-Luc.…”

Fluorescence, ultrasonic and photoacoustic imaging for analysis and diagnosis of diseases

“…By taking into account the merits of bacterial systems, Sun and co-workers developed a type of nanobacteria probe (namely Trojan nanobacteria) by combining fluorescent SiNP nanoprobes and live bacteria. 91 The developed Trojan nanobacteria simultaneously possess the optical properties of SiNPs and the BBB penetrability of bacteria, and are therefore suitable for in vivo multi-modal imaging and combined therapy of tumors in the brain or deep tissues. 91,92 In 2022, through surface modification with the BBB-targeting ligand glucosamine (G), the same group further developed a kind of nanoprobe with BBB-targeting ability, which was made from G-modified SiNPs loaded with ICG molecules (G-ICG-SiNPs).…”