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The core value of this paper published in Nature Communications, reported by Qiao Haishi from China Pharmaceutical University, Jia Lizhou from the Central Laboratory of Baianqiao Hospital in Inner Mongolia, Yu Dahai from Nanjing University of Chinese Medicine Affiliated Jiangsu Provincial Hospital, and Ren Ke from Chengdu Medical College, is not merely "creating a coated BCG", but rather it presents a concept with deeper mechanistic depth: by engineering BCG to specifically reprogram tumor-associated macrophages (TAM) and induce trained immunity, it repositions typical "cold tumors" like glioblastoma into an immunologically activated state responsive to radiotherapy. The article does not simply regard BCG as an inflammatory stimulator; instead, it transforms it into a multifunctional biological treatment platform capable of crossing the blood-brain barrier, entering brain tumors, alleviating hypoxia, and activating the innate immune memory of TAM.
The design of this work is ingenious. The authors first used bioorthogonal chemistry to stably encapsulate the macrophage membrane onto the surface of BCG, obtaining MBCG. The purpose of this was clear: on the one hand, to enhance its stability in the body and its ability to home in on tumors; on the other hand, to leverage the camouflage properties of the macrophage membrane to enhance its ability to cross the blood-brain barrier and enter glioblastoma lesions. The article has demonstrated in both in vitro BBB models and in situ GBM models that MBCG is more likely to pass through the endothelial barrier and be taken up by TAM within the tumor than bare BCG; live imaging and in vitro organ imaging also show that the brain/tumor enrichment of MBCG is significantly better than that of the bare bacteria.
The related research, titled "Engineered BCG selectively triggers trained immunity in tumor-associated macrophages and sensitizes glioblastoma to radiotherapy in mice", was published in Nature Communications.
