Self-Propelled Nanoparticles Deliver Osteoporosis Drug Directly to Bone Cracks
By Mark Dwortzan
This research-microscope image shows the increasing density at the bone-crack site during a 40-minute test of particles that can carry the bone-healing medication. The particles were treated with a red-glowing fluorescent dye to enable the researchers to observe them. (Image courtesy of Sen laboratory, Penn State University)
A novel method for detecting and delivering healing drugs to newly formed micro-cracks in bones has been invented by a team of chemists and bioengineers at Boston University and Penn State University co-led by Professor Mark Grinstaff (BME, MSE, Chemistry).
The method uses tiny, self-powered nanoparticles, or nanomotors, to deliver the drugs directly to the cracks. The energy that revs the motors of the nanoparticles and sends them rushing toward the crack comes from a surprising source—the crack itself. As a crack emerges in a bone, minerals leach out as positively charged particles, or ions, which pull the negatively charged nanoparticles toward the crack.
Through a series of experiments co-led by Penn State Professor Ayusman Sen and described in the international chemistry journal Angewandte Chemie, the research team has demonstrated that a biocompatible nanoparticle can efficiently deliver an osteoporosis drug directly to a freshly cracked bone. In the final experiments, completed in the Grinstaff lab, BU School of Medicine graduate student Jonathan Freedman tested a common osteoporosis drug on live human bone cells.
“The treated bone cells increased in number as compared with those that were not treated with the osteoporosis drug, which confirms other studies that have shown that this drug is effective in repairing human bones,” said Grinstaff.
Unlike conventional methods, in which medications ride passively on the circulating bloodstream, where they may or may not arrive at micro-cracks in a high-enough dosage to initiate healing, the new approach promises to treat, upon formation, micro-cracks that lead to broken bones in patients with osteoporosis and other medical conditions.
“What makes our nanomotors different is that they can actively and naturally deliver medications to a targeted area,” Sen explained. “Current methods, in contrast, involve taking a drug and hoping that enough of it gets to where it is needed for healing.”
The researchers built up to their final experiments, first testing their novel way to deliver medicines to newly formed cracks in a model system using bone from a human tibia and femur and very small fluorescent particles called quantum dots made from a synthetic material. They subsequently tested their system using a natural biological material—an enzyme—which they determined could target a site on human bone and catalyze a biological reaction at the site. Finally, they demonstrated that they could attach an FDA-approved osteoporosis drug onto bio-safe “nanomotor” material that could carry it like a “nanotruck” to a crack in a human bone. When fully loaded, each nanotruck was 30 to 40 times smaller than a red blood cell.
Several more tests and further development will be needed to prove this novel method safe and effective for preventing broken bones in patients with osteoporosis and similar conditions.
Barbara K. Kennedy, director of the Penn State Eberly College of Science Office of Media Relations and Public Information, contributed to this article.
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