This report compares the properties of mono-substituted hierarchically assembled nanostructured apatitic (HANA) particles. The Mg 2+ and Si 2+ ions (1%wt) were individually substituted into an apatitic structure and produced MgHAP and SiHAP HANA particles, respectively. Besides comprehensive characterization, particles were systematically tested for their in-vitro ionic dissolution and drug-carrying abilities. Both MgHAP and SiHAP nanopowders exhibited monolithic apatitic structure, novel spherical morphology having substituted elements, mesoporous with large surface area and pore volume, and high thermal stability. Furthermore, both particles exhibited superior in-vitro bioactivity. In addition, SiHAP nanoparticles exhibited superior drug loading and sustained drug release characteristics over MgHAP particles. Thus, this study explored the potentials of novel ion-substituted HANA particles, suitable for multipurpose therapeutic applications, including tissue regeneration and drug-carrying agents.