Conclusions

Nanoparticles provide a range of new opportunities to increase the targeting of currently approved diagnostic and therapeutic agents to cancers. Improvements in targeting can lead not only to increased efficiency of these agents but also to increased signal-to-noise ratios for diagnostics and better efficacy to toxicity ratios for therapeutics. Currently, a whole new spectrum of biopharma-ceuticals and biotechnological agents for cancer diagnosis and therapy are also being developed. Some of these materials require special formulation technologies to overcome drug-associated problems. Although nanoparticles offer improved profiles for some currently approved diagnostic and therapeutic agents, many biotechnology-based materials absolutely require some method of delivery that compensates for their poor stability or non-selective activity in a systemic setting. Nanoparticles offer a set of new opportunities for the development of these agents.29

Nanoparticles can be prepared in such a way as to have diagnostic or therapeutic agents integrated into them in ways that either freely releases the agents or that requires decomposition of the nanoparticle for the release to occur. Because of the inherent nature of small (nanometer-sized) structures, the body can identify and respond to these as foreign. Such a response can by suppressed by incorporation of agents that might suppress undesirable responses, or the application can be matched to the nanoparticle to make use of these natural responses. It is even possible to modify these natural responses to better match the desired clinical outcome. Specific components used to prepare nanoparticles can affect not only their stability in the body but also their capacity to be absorbed across natural barriers of the body (e.g., BBB) as well as the inherent systemic distribution of the nanoparticle that might compete with or complement efforts to selective targeting strategies.

Without the current fanfare related to nanotechnologies, nanoparticles have been used to selectively target a number of organs of the body for a number of years. Nanoparticle colloids were shown to have contrast media properties that related to the unique surface properties of cells in specific organs of the body.139 Deviations from normal function such as oncogenic transformation can lead to changes in a cell's surface properties and its capacity to interact with nanomaterials. For example, gadolinium-based nanoparticles are taken up by hepatocytes, and by the decreased function and density of cancer cells in the liver tumors, a reduced level of uptake of these particles can be used to identify tumors using Tl-weighted images obtained from MRI.42

Throughout this chapter, there has been frequent referral to viral infection events as a paradigm for cellular and intracellular targeting strategies for nanoparticles. Indeed, these materials are very successful models for nanoparticle targeting because they have developed mechanisms to discriminate between the various cells of the body (e.g., tropism for only cells of the intestinal tract) and can deliver labile (polynucleic acids) payloads that dramatically affect cell function. In response to these nanoparticle invaders, host cells have established intricate and complicated mechanisms that block viral infectivity and cellular actions. Such evolutionary pressures have led to the incorporation of intricate and novel methods by viruses to effectively combat these protective systems established by host cells. It is into this environment where the virus nanoparticles and host cells have battled back and forth for millennia that efforts to use nanoparticles to deliver agents to cancers for diagnosis and/or therapy must be framed.

Finally, it is important to sound a precautionary note for the potential to over-engineer nano-particles. Nanoparticles provide a platform that can potentially be used to simultaneously function in targeting therapeutic molecules as well a reporter and/or imaging agents. Elegant studies have been performed with nanoparticles modified three, four, or even five times with materials that promoted active targeting and/or reduced non-specific targeting as well as corrected undesirable properties of residence, biodistribution, and stability. Such tour-de-force efforts would be considered unrealistic by pharmaceutical companies for scaling to a process that would gain approval from regulatory agencies. Clinical success can be demonstrated for a nanoparticle system only if it can get to the clinic; a viable production process is critical to this development path. Therefore, successful applications of nanoparticles in target cancers for therapy and diagnosis will require designing systems where the inherent activities and distribution of nanoparticle size and composition allow for minimal modifications that will translate into production process steps.

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