Nanoparticles built from rapamycin shrink venous malformations in mice

Researchers at Boston Children's Hospital have developed nanoparticles that deliver medication directly to venous malformations, abnormal tangles of veins that can grow with a child and become disfiguring or life-threatening. Current treatments include surgery, which carries a high risk of blood loss for large malformations, and oral rapamycin, which can cause side effects that lead patients to stop taking it.

The team, led by Dr. Daniel Kohane, Dr. Kathleen Cullion, and postdoctoral fellow Dr. Weimin Tang, hypothesized that the leaky nature of malformed vessels would trap nanoparticles injected into the bloodstream. They engineered a new type of particle by linking many rapamycin molecules into a polymer structure, forming the nanoparticle itself rather than merely encapsulating the drug.

Gaps within these rapamycin-based spheres were then loaded with ponatinib, a second drug that inhibits pathways involved in vessel overgrowth. This design allows the particle to exert therapeutic effects through its own structure while simultaneously delivering a complementary agent.

In mouse models of venous malformation, a single intravenous injection of the dual-drug nanoparticles reduced malformation volume by 70 percent after 20 days. Mice treated with the same two drugs given orally showed a significantly smaller reduction.

The researchers note that because the nanoparticle is made of rapamycin, it retains drug-like activity without needing to release free molecules, a feature that may reduce systemic exposure. The formulation could potentially be adapted for other conditions characterized by leaky vasculature.

The team plans to conduct longer-term studies to determine whether the effect is durable or if additional doses are required to eliminate the malformations completely. The findings were published in Science Translational Medicine.