Hierarchically Structured Hydroxyapatite Particles Facilitate the Enhanced Integration and Selective Anti-Tumor Effects of Amphiphilic Prodrug for Osteosarcoma Therapy.

Efficient delivery of cargo into target cells is a formidable challenge in modern medicine. Despite the great promise of biomimetic hydroxyapatite (HA) particles in tissue engineering, their potential applications in bone tumor therapy, particularly their structure-function relationships in cargo delivery to target cells, have not yet been well explored. In this study, we developed biomimetic multifunctional composite microparticles (Bm-cMPs) by integrating an amphiphilic prodrug of curcumin with hierarchically structured HA microspheres (Hs-hMPs). Then, we determined the effects of the hierarchical structure of vehicles on the integration and delivery of cargo as well as the anti-osteosarcoma (OS) effect of the composite. Different hierarchical structures of the vehicles strongly influenced the self-assembly behavior of the prodrug. The flake-like crystals of Hs-hMPs enabled the highest loading capacity and enhanced the stability of the cargo. Compared to the normal cells, OS cells exhibited 3.56-times better uptake of flake-like Hs-hMPs, facilitating the selective anti-tumor effect of the prodrug. Moreover, Bm-cMPs suppressed tumor growth and metastasis by promoting apoptosis and inhibiting cell proliferation and tumor vascularization. Our findings shed light on the potential application of Bm-cMPs and suggest a feasible strategy for developing an effective targeted therapy platform using hierarchically structured minerals for OS treatment. This article is protected by copyright. All rights reserved.