Designed bone-targeting ROS-responsive nanoplatform for precision glycolysis inhibition in postmenopausal...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacology

Background:

• Postmenopausal osteoporosis (PMOP) results from estrogen deficiency, leading to increased bone resorption.
• Glycolysis and lactate transport via monocarboxylate transporters (MCTs) are critical for osteoclast activity.
• MCT inhibition, using drugs like AZD3965, is a potential therapeutic strategy for PMOP.

Purpose of the Study:

• To develop a bone-targeted, reactive oxygen species (ROS)-responsive nanocarrier (PH/DPA@A) for AZD3965 delivery.
• To evaluate the in vitro and in vivo efficacy of PH/DPA@A in treating PMOP.

Main Methods:

• Engineered a nanocarrier integrating a bone-targeting ligand (DPA) and a ROS-cleavable shell (PH) to encapsulate AZD3965.
• Assessed nanoparticle characteristics, drug release kinetics, and in vitro osteoclast inhibition.
• Evaluated in vivo bone targeting, bone mineral density, and microarchitecture in ovariectomized (OVX) mice.

Main Results:

• Nanoparticles showed controlled ROS-triggered drug release and high bone-targeting efficiency.
• PH/DPA@A effectively inhibited osteoclast formation and bone resorption in vitro.
• In vivo administration to OVX mice increased bone mineral density and improved trabecular bone structure.

Conclusions:

• The PH/DPA@A nanoplatform enables efficient targeted delivery of AZD3965 to osteoporotic bone.
• This approach demonstrates significant therapeutic potential for managing postmenopausal osteoporosis.