One key challenge in the therapy of glioblastoma (GBM) is to develop a high-efficiency drug delivery system (DDS) bypassing the blood-brain barrier (BBB), which is impermeable to most drugs. To delivery drugs into brain, invasive and non-invasive technologies have been proposed. The invasive approaches include deep brain stimulation, intracerebral grafts, direct brain injection, intrathecal brain delivery and so forth. Due to the huge risks and pains caused by the invasive approaches, people are turning more and more attention to the non-invasive approaches, which include receptor-mediated transcytosis, the use of neurotropic viruses, exosomes, nanoparticles and so on. On the other aspect, bacteria recently have achieved encouraging outcomes in cancer therapy. Conceptually, bacteria for cancer treatment are independent of ‘genetic makeup’, featuring superior merits over conventional treatments including intrinsic tumour navigation ability, tumour tissue-penetration ability as well as gene packaging ability. Remarkably, it has been well demonstrated that bacteria can cross the BBB transcellularly, paracellularly and/or in infected phagocytes, which is the basis of bacterial systems for the treatment of GBM. However, GBM therapies with live bacteria are still few, since they encounter numerous challenges, such as difficulty in precise control of drug release, inadequate stimulation to immune responses, and potential bacterial toxicity (e.g., bacteremia). Intriguingly, there are increasing enthusiasms for developing bacteria-nanoparticles hybrid systems for the drug delivery against other types of cancer. However, in these systems, the nanoparticles are generally loaded on the surface of bacteria. Moreover, the surface loaded nanoparticles might break the integrity of the capsule of bacteria, and the intact capsule can prevent fusion of bacteria with lysosomes, which is necessary for traversal of the BBB as live bacteria.
To address this problem, Prof. Houyu Wang and Prof. Yao He et al. from Suzhou Key Laboratory of Nanotechnology and Biomedicine & FUNSOM, Soochow University recently have leverage bacterial specific ABC transporter to deliver glucose polymer (GP), indocyanine green (ICG)-modified silicon nanoparticles (GP-ICG-SiNPs) into bacterial cells to develop an innovative bacteria-based drug delivery system (dubbed Trojan bacteria) based on their previous work (Nat. Commun. 2019, 10, 4057; Nat. Commun. 2022, 13, 1255; Angew. Chem. Int. Ed. 2022, 61, e202208422). In an orthotopic GBM mouse model, they demonstrate that the intravenously injected Trojan bacteria could take therapeutics together not only to bypass the BBB, but also to target and penetrate GBM tissues. Under an 808 nm-laser irradiation, the photothermal effects (PTT) produced by ICG allow the destruction of Trojan bacterial cells and the adjacent tumour cells. Furthermore, the bacterial debris as well as the tumour-associated antigens would promote antitumor immune responses that prolong the survival of GBM-bearing mice. The related results were published in Nature Communications (Nat. Commun. 2022, 13, 5127). The first authors of this article are Miss Rong Sun and Miss Mingzhu Liu.
Link to article: https://www.nature.com/articles/s41467-022-32837-5
Title: Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy.
Authors: Rong Sun, Mingzhu Liu, Jianping Lu, Binbin Chu, Yunmin Yang, Bin Song, Houyu Wang* & Yao He*
Project funding: The authors acknowledge financial support from National Natural Science Foundation of China (No. 21825402 and 22074101), Natural Science Foundation of Jiangsu Province of China (No. BK20191417), the China Postdoctoral Science Foundation (No. 2021M692347) and the Program for Jiangsu Specially-Appointed Professors to the Prof. Yao He, a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), 111 Project as well as the Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC).
Editor: Guo Jia