Next-generation nanomedicine

In an article featured on the cover of the March issue of Nature Nanotechnology, Mauro Ferrari, Ph.D., of The University of Texas Health Science Center at Houston, presented a proof-of-concept study on a new multistage delivery system (MDS) for imaging and therapeutic applications. This discovery could go a long way toward making injectable drugs more effective.

"This is next-generation nanomedicine," said Ferrari, who played a critical role in the development of the National Cancer Institute’s (NCI) Alliance for Nanotechnology in Cancer. “Now we’re engineering sophisticated nanostructures to elude the body’s natural defenses, locate tumors and other diseased cells, and release a payload of therapeutics, contrasting agents, or both over a controlled period.”

Nanotechnology offers new and powerful tools to design and engineer novel drug delivery systems and to predict how they will work once inside the body. “The field of therapeutic nanoparticles began with tiny drug-encapsulated fat bubbles called liposomes, now commonly used in cancer clinics worldwide. Targeting molecules were later added to liposomes and other nanovectors to assist in directing them to diseased cells,” Ferrari said.

Getting intravenous agents to their intended targets is no easy task. It is estimated that approximately 1 of every 100,000 molecules of agent reaches its desired destination. Physicians are faced with the quandary of increasing the dosage, which can lead to side effects, or reducing the dosage, which can limit the therapeutic benefits.

The multistage approach, according to Ferrari, is needed to circumvent the body’s natural defenses or biobarriers, which act as obstacles to foreign objects injected in the bloodstream. “To overcome this problem, we hypothesized and developed a multifunctional MDS comprising stage 1 mesoporous particles loaded with one or more types of stage 2 nanoparticles, which in turn can carry either active agents or higher stage particles. We have demonstrated the loading, controlled release, and simultaneous in vitro delivery of quantum dots and carbon nanotubes to human vascular cells,” said Ferrari.

In addition to circumventing biobarriers, Ferrari’s team is working on the biochemical modifications required to efficiently deliver the MDS to a specific cancer lesion. “We have preliminary data that show that we can localize a payload of diagnostic agents, therapeutic agents, or combination of both to target cells. Once on site, the molecules can be released in a controlled way, and then the MDS will degrade in 24 to 48 hours, be transformed into orthosilicic acid, and leave no trace in the body,” Ferrari said.

One of Ferrari’s coauthors, Ennio Tasciotti, Ph.D., said the proof-of-concept study would not have been possible without a multidisciplinary effort that included contributions from mathematicians, physicists, engineers, chemists, and biologists. “We are dealing with objects that are in the billionth of a meter size range, and to study such objects we used cutting-edge technologies,” Tasciotti said. "The characterization of the particles was performed using scanning electron and atomic force microscopy, dynamic light scattering, fluorimetry, and flow cytometry. The interaction of particles with cells was studied using fluorescence and confocal microscopy as well as a series of assays intended to determine cell viability and internalization rate of the nanoparticles."

This work, which was supported in part by the NCI, is detailed the paper “Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications.” Investigators from The University of Texas M. D. Anderson Cancer Center and Rice University also participated in this study. An abstract of this paper is available at the journal’s Web site. http://nano.cancer.gov