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

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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… Click to show full abstract

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.

Keywords: hydroxyapatite particles; selective anti; hierarchically structured; therapy; amphiphilic prodrug; tumor

Journal Title: Advanced healthcare materials
Year Published: 2023

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