Normalized Tumor Blood Vessels Facilitate Drug Delivery
(ChemotherapyAdvisor) – Normalized blood vessels in tumors facilitate delivery of nanoparticle-based oncology drugs, according to researchers at Harvard Medical School and Massachusetts General Hospital. The study, entitled “Normalization of tumor blood vessels improves the delivery of nanomedicines in a size-dependent manner” was published in Nature Nanotechnology and appeared online on April 8.
This study was based on several facts: Tumor blood vessels are leaky and poorly organized, which reduce blood supply to them, and consequently, impair drug delivery. Anti-angiogenic therapies ‘normalize' the abnormal blood vessels in tumors and thus improve the delivery and effectiveness of chemotherapeutics with low molecular weights. The researchers aimed to determine if normalizing tumor vessels can improve the delivery of nanomedicines.
The researchers demonstrated that repairing the abnormal vessels in mammary tumors, by blocking vascular endothelial growth factor receptor-2, improves the delivery of smaller nanoparticles (diameter, 12nm) while hindering the delivery of larger nanoparticles (diameter, 125nm). Mathematical models were also utilized to demonstrate that reducing the sizes of pores in the walls of vessels through normalization allows small nanoparticles to enter them more rapidly.
The authors concluded: “Smaller (~12nm) nanomedicines are ideal for cancer therapy due to their superior tumor penetration.”
"We found that vascular normalization only increases the delivery of the smallest nanomedicines to cancer cells," says Vikash P. Chauhan, of the Steele Laboratory of Tumor Biology in the MGH Radiation Oncology Department, lead author of the report. "We also showed that the smallest nanomedicines are inherently better than larger nanomedicines at penetrating tumors, suggesting that smaller nanomedicines may be ideal for cancer therapy."