Bone Destruction-Chemotactic Osteoprogenitor Cells Deliver Liposome Nanomedicines for the Treatment of Osteosarcoma and Osteoporosis

Abstract

Therapeutic efficacy of skeletal diseases is usually limited by unfavorable drug delivery due to incapable bone targeting and low bone affinity of conventional drug carriers, as well as relatively reduced vascularization and dense structure of bone tissues. Due to CXC chemokine receptor 4 (CXCR4)/CXC chemokine ligand 12 (CXCL12) signal axis-guided recruitment, osteoprogenitor cells (OPCs) can actively migrate to bone disease nidus. Here, drugs-loaded nanoliposomes are prepared and decorated onto OPCs by biotin-streptavidin linkage for precise bone disease targeting and effective drug delivery. In mouse models of tibia defect and orthotopic osteosarcoma, superior targeting property of OPCs-based drug delivery systems toward diseased bone niduses is verified. By encapsulating antitumor and antiosteoporosis drugs into nanoliposomes, OPCs-based drug delivery systems effectively inhibit disease development and restore bone destruction in mouse models of orthotopic osteosarcoma and ovariectomized osteoporosis. This study reveals a cell-based drug delivery system for precise bone disease targeting and highly effective drug delivery, which will find great potential as a universal drug delivery platform for targeting treatment of various bone diseases.

Keywords: bone disease; bone targeting; cell-based drug carrier; nanomedicine; osteoprogenitor cell.