In conclusion, we prepared a DDS consisting of ALN-conjugated NPs to deliver DTXL and siRNA, and used it in a mouse PCa bone metastasis model to demonstrate its feasibility in vivo, besides evaluating its in vitro antitumor effects (DTXL + siRNA)@NPs-ALN showed improved bone-targeting capacity, inhibited osteoclast differentiation and promoted osteoblast differentiation mainly by affecting the SHH paracrine signaling in the bone microenvironment. The gene discussed is ARLN; the disease is posterior cortical atrophy.