New nano-based technology is a glimmer of hope for osteoporosis treatment

Researchers at the University of Central Florida have developed a novel method of treating osteoporosis that delivers medication to specific parts of the body using nanobubbles. By using ultrasound-responsive nanobubbles, it's possible to treat patients' targeted areas without any side effects such as osteonecrosis (delayed healing of the jawbone) and gastrointestinal problems.

Mentioned by UCF, Mehdi Razavi, an assistant professor in the UCF College of Medicine and a member of the university's Biionix Cluster, and UCF biomedical sciences student Angela Shar created the new technology as part of the lab's focus on creating tools for therapies and diagnostics.

Understanding osteoporosis

Low bone mass, micro-architectural degeneration of bone tissue that causes bone fragility, and an elevated risk of fractures are all symptoms of osteoporosis, a systemic skeletal condition. The mineral density per unit volume of bone has decreased. Therefore, bones become more easily broken. Although it is most commonly seen in the vertebrae, hip, and wrist bones, all bones in the body are affected by this condition. Although it can be seen in both sexes, 80 percent of the patients are women. In addition, it is the most frequent cause of a broken bone in elderly people.

Razavi says that a healthy body continually replaces old or damaged bone tissue at a steady rate to ensure good bone quality and mass.

"But when the rate of bone resorption becomes higher than bone formation, then it leads to osteoporosis, a systemic disease of the skeletal system," he says.

"There are a lot of nanoplatforms out there for osteoporosis treatment. But the advantage of ultrasound-responsive nanobubbles is that they require ultrasound for bubble disruption and gene delivery. Ultrasound itself can actually facilitate bone formation," Razavi also adds.

Bisphosphonates are the most commonly used osteoporosis drugs in patients who are found to be at high risk of developing fractures in their bones. Common side effects of medications containing bisphosphonates include abdominal pain, nausea, and heartburn. On the other hand, maybe most importantly, it causes osteonecrosis of the jaw (ONJ).

A severe bone disease affecting the maxilla and mandible, ONJ brings about unhealing mouth ulcers. Additionally, there may or may not be discomfort, swelling of the soft tissue in the area, subsequent infection, or drainage.

A viable, safe alternative, the UCF invention both treats and prevents the effects of osteoporosis.

"It is a dual-acting technology," Razavi says. "On one side, you are reducing bone resorption, and on the other side, you are increasing bone formation using ultrasound."

The nanobubbles target osteoclast cells

The nanobubbles in one example application convey the osteoporosis-related silencing or knockdown gene, cathepsin K small interfering ribonucleic acid (CTSK siRNA).

According to Razavi, the nanobubbles target osteoclast cells, which are the bone cells that carry the CTSK gene, while also shielding the siRNA from coming into direct contact with its surroundings. The process of bone resorption depends heavily on CTSK.

He continued, "The delivery system also aids in slowing the release of the medication and extending the efficiency of the gene silencing mechanism."

"The gas core helps us to image and track the nanobubbles," Razavi says. "It's also embedded with molecules that can target bone."

"The bubbles go into the bone cells, search and find those genes that cause osteoporosis, and they bury the CTSK siRNA, which then creates a complex," he says. "That complex is thermodynamically unstable, and that will lead to a kind of downregulation or silencing of those genes. When you measure for cathepsin K expression, you get a lower expression of that."

The study was published in Nanomedicine: Nanotechnology, Biology and Medicine on April 2022.

Study abstract:

This project aimed to develop, optimize, and test an ultrasound-responsive targeted nanodroplet system for the delivery of osteoporosis-related silencing gene Cathepsin K small interfering RNA (CTSK siRNA) for osteoporosis treatment. The nanodroplet (ND) is composed of a gas core made from perfluorocarbon, stabilized with albumin, encapsulated with CTSK siRNA, and embedded with alendronate (AL) for bone targeting (CTSK siRNA-ND-AL). Following the development, the responsiveness of CTSK siRNA-ND-AL to a therapeutic ultrasound probe was examined. The results of biocompatibility tests with human bone marrow-derived mesenchymal stem cells proved no significant cell death (P > 0.05). When the CTSK siRNA-ND-AL was supplemented with human osteoclast precursors, they suppressed osteoclastogenesis. Thus, this project establishes the potential of nanotechnology and ultrasound to deliver genes into the osteoclasts. This research also presents a novel ultrasound responsive and targeted nanodroplet platform that can be used as a gene and drug delivery system for various diseases including cancer.