Despite their great potential, full exploitation of mesoporous silica nanoparticles (MSiNPs) as in-vivo multi-functional theranostic agents is still held back by the lack of a controlled and complete biodegradability. Indeed removal of nano-medical tools from the biologic system after the accomplishment of their diagnostic or therapeutic function still remains a pivotal, yet unresolved issue impeding their clinical translation. A most desirable design for improving the properties of nano-medical tools would hence involve their ability to hierarchically self-degrade into renally clearable products after carrying out their function. Thus, the ambitious aim of this project targets the synthesis of novel, specific, hybrid MSiNPs-based theranostic tools, able to perform their beneficial action and subsequently fragment in smaller pieces allowing easy execration via renal system. In this way, thanks to the combination of the intrinsic biocompatibility of MSiNPs, their ease of functionalization and the newly conferred enhanced biodegradability, a superior material adaptable to a wide range of diagnostic and therapeutic applications, with great promise for clinical translation, will be achieved.