Multifunctional nanoparticles hold great promise for drug/gene delivery and simultaneous diagnostics and therapeutics ("theragnostics") including use of core materials that provide in vivo imaging and opportunities for externally modulated therapeutic interventions. Multilayered nanoparticles can act as nanomedical systems with on-board molecular programming done through the chemistry of highly specialized layers to accomplish complex and potentially decision-making tasks. The targeting process itself is a multi-step process consisting of initial cell recognition through cell surface receptors, cell entry through the membrane in a manner to prevent undesired alterations of the nanomedical system, re-targeting to the appropriate sub-region of the cell where the therapeutic package can be localized, and potentially control of that therapeutic process through feedback systems using molecular biosensors. This paper describes a bionanoengineering design process in which sophisticated nanomedical platform systems can be designed for diagnosis and treatment of disease. The feasibility of most of these subsystems has been demonstrated, but the full integration of these interacting sub-components remains a challenge for the field. Specific examples of sub-components developed for specific applications are described.

'Nanobiosystems' is a relatively new term describing objects in the size range below 150 nm and having structures or functions that link to biological functions. Key features are that these nanosized objects typically self-assemble, are not capable of self-replication, and have functions that take advantage of its size. Nanobiosystems can be made entirely of biological or organic molecules that are organized into nanoparticles (e.g., liposomes, dendrimers) or be totally inorganic (with the exception of surface coatings used for biocompatibility) nanoparticles (e.g., gold, iron oxide, quantum dot nanocrystals). More complex nanobiosystems are inorganic/biologic hybrid composites that may include complex multilayered structures with targeting molecules (e.g., peptides, antibodies, aptamers), cell entry-promoting molecules (e.g., HIV-tat peptide sequence), drugs (small molecules), genes (therapeutic genes, reporter genes), and core nanomaterials (e.g., gold, quantum dot, iron oxide) that give the nanobiosystems sometimes unique detection capabilities by a variety of optical and non-optical modalities (fluorescence, surface plasmon resonance, magnetic resonance imaging).

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