Modern breakthroughs in the fields of proteomics and DNA micro-arrays have widened the horizons of nanotechnology for applications with peptides and nucleic acids. Hence, biomimetic interest in the study and formulation of nanoscaled bio-structures, -materials, -devices and -therapeutic agent delivery vehicles has been recently increasing. Many of the currently-investigated functionalized bio-nanosystems draw their inspiration from naturally-occurring phenomenon, prompting the integration of molecular signals and mimicking natural processes, at the cell, tissue and organ levels. Technologically, the ability to obtain spherical nanostructures exhibiting combinations of several properties that neither individual material possesses on its own renders colloidal core-shell architectured nanosystems particularly attractive. The three main developments presently foreseen in the nanomedicine sub-arena of nanobiotechnology are: sensorization (biosensors/biodetection), diagnosis (biomarkers/bioimaging) and drug, protein or gene delivery (systemic vs. localized/targeted controlled-release systems). Advances in bio-applications such as cell-labelling/cell membrane modelling, agent delivery and targeting, tissue engineering, organ regeneration, nanoncology and immunoassay strategies, along the major limitations and potential future and advances are highlighted in this review. Herein, is an attempt to address some of the most recent works focusing on bio-inspired and -functional polymeric-based core-shell nanoparticulate systems aimed for agent delivery. It is founded, mostly, on specialized research and review articles that have emerged during the last ten years.