Hierarchically constructed selenium-doped bone-mimetic nanoparticles promote ROS-mediated autophagy and apoptosis for bone tumor inhibition

Biomimetic materials are often capable of subtly affecting tissue development, regeneration and carcinogenesis due to their high similarity to natural tissues. Despite the benefit of using such materials in tissue engineering, their prospective use in cancer therapy has been neglected, particularly the functions and mechanisms by which biomimetic materials mediate tumor suppression. Here, we prepare hierarchically constructed bone-mimetic selenium-doped hydroxyapatite nanoparticles (B-SeHANs), which recapitulate the uniaxially oriented hierarchical structure of bone HA and can potentially play a dual role in the postoperative treatment of bone tumors via the chemotherapy from selenium and the promotion of bone repair by hydroxyapatite, to systematically investigate the influence of bone-mimetic hierarchical structure in bone tumor inhibition by SeHANs in vivo and in vitro. We found that, compared to the non-biomimetic SeHANs, the B-SeHANs exhibited highly enhanced cellular internalization and intracellular degradation, and induced subsequent autophagy and caspase-dependent apoptosis via the ROS-mediated activation of the JNK pathway and inhibition of the Akt/mTOR pathway. We further verified that the B-SeHANs promoted autophagy and apoptosis to inhibit tumor growth while profoundly reducing bone destruction in a well-designed orthotopic tibial tumor model. The current work presents a feasible strategy for the development, evaluation and fundamental study of biomimetic mineral nanoparticles to inhibit tumor growth.