Multifunctional nanoparticles for drug/gene delivery in nanomedicine

Multifunctional nanoparticles hold great promise for drug/gene delivery. Multilayered nanoparticles can act as nanomedical systems with on-board "molecular programming" to accomplish complex multi-step tasks. For example, the targeting process has only begun when the nanosystem has found the correct diseased cell of interest. Then it must pass the cell membrane and avoid enzymatic destruction within the endosomes of the cell. Since the nanosystem is only about one millionth the volume of a human cell, for it to have therapeutic efficacy with its contained package, it must deliver that drug or gene to the appropriate site within the living cell. The successive delayering of these nanosystems in a controlled fashion allows the system to accomplish operations that would be difficult or impossible to do with even complex single molecules. In addition, portions of the nanosystem may be protected from premature degradation or mistargeting to non-diseased cells. All of these problems remain major obstacles to successful drug delivery with a minimum of deleterious side effects to the patient. This paper describes some of the many components involved in the design of a general platform technology for nanomedical systems. The feasibility of most of these components has been demonstrated by our group and others. But the integration of these interacting sub-components remains a challenge. We highlight four components of this process as examples. Each subcomponent has its own sublevels of complexity. But good nanomedical systems have to be designed/engineered as a full nanomedical system, recognizing the need for the other components

Design of targeted magnetic nanoparticles for multifunctional nanomedical systems

Nanomedical systems are being designed to select specific cells through biomolecular targeting and to enhance detection of diseased cells in a diverse, multicellular population. Multilayered nanoparticles are one example of a nanomedical system that has great potential for improving both cancer diagnostics and therapeutics. Functional layers constructed around a core nanoparticle are responsible for targeting nanoparticles to cells of interest, transporting nanoparticles across the cell membrane, and delivering therapeutic molecules to these targeted cells. Our current work is focused on coupling targeting molecules, including both monoclonal antibodies and synthetic peptides, to the surface of fluorescent or magnetic nanoparticles, to allow for nanoparticle targeting of cell membrane receptors expressed by cancer cell types. Both breast cancer and bladder cancer cells were used as models for nanoparticle targeting and delivery for these studies. An immunoprecipitation bioassay has indicated that antibodies remain bioactive after conjugation to the nanoparticle surface; additionally, electron microscopy has provided visual evidence that these molecules allow for the nanoparticles to gain entry across the cell membrane by receptor-mediated endocytosis. Detection of magnetic nanoparticles by MRI in tissue phantoms is being explored to understand the diagnostic potential of magnetic nanoparticle probes for the in vivo environment, while fluorescent detection and electron microscopy are being used to confirm nanoparticle internalization in vitro. The end goal of this project was to study the effects of nanoparticle dosing on cancer cells and include apoptosis-inducing peptides with the multilayered nanoparticle system, as a first approach for therapeutic strategies. These findings will contribute to the overall development of nanomedicine for treatment of disease and can be translated to other diseases that alter or infect host cells