In a study published in Science Advances, researchers from Lingang Laboratory and the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences constructed the high-resolution, whole-brain panorama of glioma vasculature, and uncovered critical details about tumor heterogeneity, blood-brain barrier (BBB) disruption, and nanoparticle (NP) distribution.

Combining the micro-optical sectioning tomography (MOST) system which visualizes brain tumors with whole-brain Nissl staining and three-dimensional reconstruction, researchers mapped pathological features of orthotopic glioma in mice at early, intermediate, and advanced stages.

They found that an unexpected invasiveness pattern. Early-stage glioma showed diffuse infiltration along host vessels, migrating up to 680 μm along the middle cerebral artery within just four days post-implantation. Then, they found vascular remodeling. Tumors progressively hijacked and remodeled host vessels, leading to dilated, disorganized, and leaky vascular networks. Besides, they found vascular mimicry (VM). Advanced tumors formed non-endothelial, channel-like structures that connected to existing vasculature, contributing to blood supply. 

Moreover, researchers found BBB Permeability. Large-diameter vessels, not just capillaries, became major sites of NP extravasation as the tumor progressed. They also visualized the distribution of angiopep-2-functionalized PLGA nanoparticles (PLGA-A2), a promising drug delivery system. They found that the NPs preferentially accumulated near leaky large vessels, with penetration depths averaging 12.19 μm. This challenges the conventional view that only capillaries facilitate drug delivery into tumors.

The study bridges the gap between cellular-level detail and whole-organ context. The multiscale atlas not only deepens our understanding of glioma biology but also provides a practical framework for designing more effective nanomedicines. Besides, this study highlights the potential of MOST/fMOST systems in pathological studies and therapeutic development, and it provides a foundation for future strategies in vascular normalization, anti-co-option therapy, and personalized medicine.