Developing a nanoparticle drug that promises to offer an alternative approach to chemotherapy with fewer side effects is a strategy that is attracting increasing interest in oncology circles. Among the many research groups worldwide involved in this field are Canadian researchers who have developed a drug-polymer conjugate that self-assembles into defined nanoparticles and, when injected, selectively accumulate in solid tumors. This promising research has attracted funding in order to set the technology along the road to eventual clinical trials.

Shyh-Dar Li, principal investigator at the Ontario Institute for Cancer Research's Medicinal Chemistry Platform group, and his team, have developed a nanoparticle formulation for docetaxel, a drug currently in clinical use to treat a number of different cancer types, including prostate, breast, lung, and ovarian cancer. The Ontario Institute for Cancer Research (OICR) and MaRS Innovation (MI), the commercialization organization for the discovery pipeline from 16 Ontario academic institutions, are providing $1.5 million in funding over a three year period to further develop this technology.

"Cellax, a drug-polymer conjugate based on proprietary NanoCMC technology provides a more targeted strategy for treating tumors, killing tumor cells while minimizing the effect on healthy tissue," Dr. Li told BioWorld Insight.

Cellax is prepared by coupling docetaxel and polyethylene glycol (PEG) to a biocompatible acetylated carboxymethylcellulose (CMC-Ac) polymer, optimized to self-assemble into defined and stable 120 nm nanoparticles.

When injected intravenously the nanoparticles selectively accumulate in tumors. "This is because the vasculature in tumors are by their very nature more permeable to nano-sized molecules than normal tissue," said Li. "All blood vessel walls are slightly porous, but in tumor cells these vessels are leaky with pores large enough for the nanoparticles to easily slip through. And we are developing Cellax to exploit this weakness."

Since in healthy blood vessels the pores are relatively small they prevent the nanoparticles from entering thereby reducing the side effects associated with conventional chemotherapy.

This is what the investigators have found in preclinical studies of the Cellax nanoparticle formulation for docetaxel delivery to metastatic tumors. The product demonstrated superior safety and efficacy compared to several approved taxane therapeutics, including Taxotere and Abraxane (albumin-bound paclitaxel; the only FDA-approved taxane nanoparticle).

With their new funding, Li and his team will produce near clinical grade quantities of the drug for the toxicology and other studies necessary to file a clinical trials application with Health Canada to test Cellax in clinical trials in cancer patients.

They will be initially targeting breast, prostate and pancreatic cancers with clinical trials anticipated to begin in 2015, Li added.

Although it is still early days for the Canadian research team and for nanoparticle research in general some clinical work in currently ongoing.

For example, a clinical trial has demonstrated that Oncoprex (TUSC2 nanoparticles), developed by Genprex Inc., of Austin, Texas, can be safely administered in advanced lung cancer patients to halt cancer or shrink primary and metastatic tumors in some patients.

Thirty-one late-stage lung cancer patients, unresponsive to prior therapy, were treated with Oncoprex monotherapy at six escalating dose levels evaluating safety. Twenty-three patients received two or more doses of Oncoprex and were eligible for evaluation. Tumor growth was halted in five patients, with tumor shrinkage or reduced metabolic tumor activity observed in both primary and metastatic tumors in liver and pancreas. Before and after tumor biopsies showed 10- to 25-fold increases of TUSC2 protein after treatment. (See BioWorld Today, April 27, 2012.)