Breaking through the basement membrane barrier to improve nanotherapeutic delivery to tumours

An effective nanotherapeutic transport from the vasculature to the tumour is crucial for cancer treatment with minimal side effects. Here we demonstrate that, in addition to the endothelial barrier, the tumour vascular basement membrane surrounding the endothelium acts as a formidable mechanical barrier that entraps nanoparticles (NPs) in the subendothelial void, forming perivascular NP pools. Breaking through this basement membrane barrier substantially increases NP extravasation. Using inflammation triggered by local hyperthermia, we develop a cooperative immunodriven strategy to overcome the basement membrane barrier that leads to robust tumour killing. Hyperthermia-triggered accumulation and inflammation of platelets attract neutrophils to the NP pools. The subsequent movement of neutrophils through the basement membrane can release the NPs entrapped in the subendothelial void, resulting in increased NP penetration into deeper tumours. We show the necessity of considering the tumour vascular basement membrane barrier when delivering nanotherapeutics. Understanding this barrier will contribute to developing more effective antitumour therapies. Nanoparticle penetration into tumours is an obstacle to cancer therapeutics. Here the authors show that the tumour vascular basement membrane constitutes a barrier that reduces nanoparticle delivery and demonstrate an immune-driven strategy to overcome the barrier, increasing nanoparticle movement into tumours.

Automated summary

This study identifies the tumour vascular basement membrane as a barrier to nanoparticle delivery and proposes an immune-driven strategy to overcome this barrier, increasing nanoparticle movement into tumours.