POSS-based nanostructures for biomedicine: from design to therapeutic potential

Polyhedral oligomeric silsesquioxane (POSS), with its well-defined hybrid organic-inorganic cage architecture, has emerged as a versatile nano-building block for engineering advanced nanostructures. This review focuses specifically on free-standing POSS-based nanostructures, distinct from the extensively covered hydrogels or scaffolds, to systematically examine their synthesis, properties and biomedical applications. The synthetic methodologies and fundamental properties of POSS, which form the basis for its utility in nanostructure design, are introduced first. Next, we highlight how these nanostructures leverage the rigid POSS to achieve exceptional stability, high functionalization density, controlled self-assembly and improved theranostic performance. A separate section is devoted to POSS-based dendrimers, given their unique architectural precision. Several key roles of POSS in targeted drug delivery, improved bio-imaging and long-term anti-biofouling have been outlined. Despite the promising advances, we critically address key challenges hindering clinical translation, including synthetic reproducibility, long-term toxicity and biodegradability concerns. This overview aims to provide a focused perspective on POSS-based nanostructures, bridging material design with biomedical potential while outlining pathways toward future therapeutic and diagnostic platforms.