Provided herein are compositions, systems, kits, and methods for treating cancer in at least one bone of a subject using nanoparticles encapsulating, or conjugated to, an anti-cancer agent. In other embodiments, provided herein are composition, systems, kits, and methods for treating a bone disease (e.g., osteoporosis) in a subject using nanoparticle encapsulating, or conjugated to, a RANKL inhibitor. The nanoparticle are, in certain embodiments, neutral or nearly neutral in charge (e.g., zeta potential between −；5 and +5 mV) and less than 250 nm in diameter on average (e.g. have an average diameter between 100 and 200 nm).
