Abstract
Nanoparticles designed to deliver docetaxel to prostate cancer cells while sparing healthy tissue have shown promise in the early stages of a phase I clinical trial in 12 patients.
Nanoparticles designed to deliver docetaxel to prostate cancer cells while sparing healthy tissue have shown promise in the early stages of a phase I clinical trial in 12 patients, in work by researchers at BIND Biosciences and their colleagues (Sci Transl Med 2012; 128:128–39). The agent, which binds to cells expressing prostate-specific membrane antigen (PSMA), shrunk tumors in 2 patients.
BIND Biosciences, based in Cambridge, MA, also reported that the targeted nanoparticle (known as BIND-014) performed well in preclinical studies, with mean tumor weight in a mouse model of human prostate cancer regressing by 26% over 7 weeks without toxic effects. During the same time period, the tumors of such mice given conventional docetaxel grew by 100%. Additionally, the pharmacokinetics of the nanoparticle-encapsulated drug were similar in mice, rats, and monkeys, a good sign that the drug will behave the same way in humans.
At the core of the drug is a polymer sphere loaded with docetaxel. Jutting from the surface is a coating of polyethylene glycol molecules, which serves 2 purposes. The polymer coating helps the drug circulate in the bloodstream. Also, at the tips of some of these polyethylene glycol molecules are ligands that bind tightly and specifically to PSMA, which is found on prostate tumor cells and on their vasculature.
BIND Biosciences combinatorially creates large libraries of nanoparticle-encapsulated drugs, each with slightly different properties. Researchers then test the resulting designs in rodents, and iteratively redesign the ones that perform the best, until a drug with good performance emerges.
With BIND-014′s basic nanoparticle-encapsulated delivery structure in place, the company expects to develop targeted therapies for other diseases in fewer steps, by plugging in different drugs and cell-targeting molecules.
The potential benefits of nanomedicine “are vast but the complexity of the system can be vast, too,” says Sara Hook, PhD, a projects manager in the National Cancer Institute's office of Cancer Nanotechnology Research. There are many parameters to tune—for example, how hydrophobic, rigid, big, or small the particle is; how it's attached to the drug; and how it will bind to target cells. It's also difficult to predict how changing each of these properties will affect a nanoparticle drug's behavior in the body.
The positive early results with BIND-014 demonstrate the promise of BIND Bioscience's approach in addressing these challenges, Hook says.
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