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This work, reported by Professor Zhang Mingjun from the School of Biomedical Engineering at Tsinghua University, Professor Wang Yilong from Beijing Tiantan Hospital affiliated to Capital Medical University, and the National Clinical Research Center for Neurological Diseases, and co-first authors Gao Xizhe, Liu Xiangrong, and Wang Nanxing, proposes a "new concept of cranial-targeted drug delivery through the synergy of skull, immunity, and nanoparticles". The authors did not attempt to modify the drugs to "force their way" through the blood-brain barrier (BBB), but instead modified the delivery route: They directly injected drug-loaded albumin nanoparticles into the bone marrow of the skull (ICO), allowing these nanoparticles to "hijack" the cranial bone marrow immune cells (mainly neutrophils and monocytes) in situ. These cells inherently have the function of monitoring brain inflammation and can migrate along the natural "immune shortcut" of cranial bone-meningeal microchannels (SMCs) to the meninges and even the lesion boundary, thereby bypassing the BBB and achieving targeted delivery to the lesion site.
In terms of mechanism, the albumin nanoparticles are efficiently phagocytosed by myeloid cells through complement-mediated opsonization; in the case of stroke or neuroinflammation, these "drug-loaded immune cells" are strongly mobilized by chemical chemotactic signals, carrying the drugs through the SMCs into the damaged brain region, and can transfer the nanoparticles to neurons. Using the model drug neuroprotector peptide NA1 (nerinetide), the authors demonstrated that the ICO approach + cell-mediated delivery can achieve efficacy even better than intravenous administration with only 1/15 of the dose, significantly reducing infarct volume, alleviating brain edema, protecting white matter structure, and improving long-term cognitive and motor functions.
More importantly, the team conducted the first exploratory clinical trial (SOLUTION) to verify the feasibility and safety of the ICO operation in patients with malignant middle cerebral artery infarction: The surgery was controllable, the complications were acceptable, no significant safety disadvantages were observed in the 90-day follow-up, and there was a trend of improvement in NIHSS. Overall, this is a systematic strategy of "material-driven immune cell carrier + skull immune pathway + precise lesion delivery", breaking through the limitations of the traditional BBB, providing a new translatable drug delivery path for various neurological diseases.
Repost：https://mp.weixin.qq.com/s/fKUrvd9kEdVRsPA2P5SkPQ
