Surgeons, pathologists, biomedical engineers and chemists from Boston University and Harvard Medical School used specially-formulated expanding nanoparticles to deliver high doses of the drug paclitaxel into mice with malignant mesothelioma.
By loading the drug into nanoparticles that expand in the presence of low pH, they were able to specifically target mesothelioma cells and dramatically impact mesothelioma survival without triggering dose-limiting side effects.
Targeting Mesothelioma Cells with Nanoparticles
A nanoparticle is a man-made microscopic particle smaller than 100 nanometers in size. These particles have numerous applications in electronics and optics but, in medicine and cosmetics, their primary function is delivery.
Standard nanoparticles do not target any particular kind of tissue. But the nanoparticles used for this new mesothelioma treatment were designed to expand and release their contents only when exposed to a certain pH level.
Because cancer is known to thrive in an acidic (low pH) environment and cannot survive in a normal, more alkaline environment, these so-called expansile nanoparticles (eNPs) can be used to deliver medicine right to the site of peritoneal mesothelioma tumors.
Mesothelioma Survival Benefits of Nanoparticle Delivery
Most mesothelioma patients are treated with chemotherapy. And yet, most mesothelioma patients still die of their illness within 18 months of diagnosis. Part of the problem is that it is often not possible to deliver a high enough dose of medication to kill the mesothelioma cells without also doing irreparable harm to normal, healthy cells.
The expansile nanoparticle delivery system gets around the problem by delivering the lethal drugs only in the presence of tumors, thereby limiting the negative impact on normal tissue.
In the new Harvard study, researchers used eNPs to deliver the cytotoxic drug paclitaxel to peritoneal mesothelioma tumors in the abdomens of mice.
Remarkable Mesothelioma Treatment Results
The researchers found that, not only did the eNPs “rapidly and specifically localize to tumors” within just four hours of injection, but that the tumors quickly absorbed the drug and retained it for more than two weeks.
“As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles,” writes thoracic surgeon Rong Liu, MD, PhD, of Brigham and Women’s Hospital.
The new report is published in in the journal Biomaterials.
Liu, R, et al, “Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma”, September 2016, Biomaterials, pp. 175-186