Precision targeting of SRC signaling in glioblastoma: Mechanistic insights and bilosome nanotechnology

The most aggressive and treatment-resistant primary brain malignancy is glioblastoma (GBM). It spreads widely throughout the brain, grows rapidly, and often does not respond to conventional therapies. The aberrant activation of SRC, a non-receptor tyrosine kinase, is a major factor in GBM development. The SRC Paradox, a sharp divergence in which strong molecular suppression in vitro fails to translate into clinical efficacy because of the blood-brain barrier's (BBB) restrictive kinetics, has historically hampered the translational trajectory of SRC inhibitors in GBM. This paper reassesses the SRC tyrosine kinase as a crucial orchestrator of GBM invasiveness, whose therapeutic potential remains constrained by physiological barriers rather than merely acting as a redundant signaling node. To overcome this translational impasse, we propose the crucial integration of bilosomes, which are bile-salt-stabilized vesicular nanocarriers. In contrast to conventional liposomal systems, bilosomes' distinct amphiphilic structure and greater membrane flexibility may enhance BBB permeation and cellular uptake while protecting SRC inhibitors from metabolic breakdown and systemic sequestration. We also analyze the molecular interactions between the glioma microenvironment and bilosomal surface functionalization. This review lays a rigorous foundation for the next generation of CNS-specific nanomedicines by integrating current advances in bilosomal pharmacokinetics with the basic biology of SRC-mediated oncogenic signaling, turning the "SRC Paradox" into a solid clinical reality.