Two groups of researchers at the Children’s Hospital of Philadelphia (CHOP) led by Garrett M. Brodeur, M.D., a pediatric oncologist and expert in neuroblastoma; and a group of CHOP nanotechnology researchers led by Michael Chorny, Ph.D., have developed biodegradable nanoparticles which can precisely deliver anticancer drugs to attack neuroblastoma. Their work has been published in Cancer Letters and Biomaterials respectively.
Neuroblastoma is a deadly cancer which affects the peripheral nervous system of children causing solid tumors. The cure rates for this cancer lags behind most other pediatric cancers.The numero uno challenge in cancer research has always been to deliver drugs to the cancerous tissue while leaving the healthy tissues intact.
This study used ultra small nanoparticles, less than 100nm in diameter (much tinier than red blood cells) to penetrate the tumor and deliver the therapeutic drug, SN38 – the active form of irinotecan, a conventional anticancer drug used to treat neuroblastoma.
“We can also adjust their composition to keep the active molecule entrapped in a polymer until nanoparticles reach the targeted tumor, and customize the timing of the polymer’s breakdown to allow controlled release of SN38 over a time scale that provides the best therapeutic effects,” says Chorny.
In laboratory mice, they compared results obtained from the nanoparticle encapsulated SN38 to those using a comparable dose of irinotecan. The nanoparticle delivery of SN38 prodrug to the tumor was 100-fold higher than irinotecan alone, with a sustained drug presence for about 72 hours and showed nil toxicity in mice. These nanoparticles helped them achieve greater efficacy at lower total doses.
In addition, most of the mice survived tumor-free for over 6 months after nanoparticle delivery, whereas all the mice treated with irinotecan had tumor recurrence shortly after treatment stopped, and they all died shortly after.
“The nanoparticles are designed to slowly deliver a drug to the tumor, where it kills multiplying cancer cells, with lower toxicity to the systemic circulation”, said Brodeur.
Chorny’s group described how the team engineered the specially formulated nanoparticles. They exploited the uniqueness of tumors- in general. They exhibit tissue leakiness or show EPR effect meaning enhanced permeability and retention.
“Tumor blood vessels are more leaky and disorganized than blood vessels in normal tissue. In healthy tissue there are tight junctions in blood vessels,” he said. “But tumors don’t have those tight junctions and have inefficient circulation, so the nanoparticles we deliver bypass healthy tissues, but accumulate in tumors where they release the anticancer agents.”
Brodeur aims to translate these preclinical results to human trials within the next year. “We envision targeted delivery via nanoparticles as a fourth arm of targeted cancer therapy,” he said.
If this technique achieves considerable clinical success, then it could strengthen the available approaches for treating childhood cancers. It could also have wider applications such as treatment of other cancers currently treated using irinotecan.