Introduction

Nanotechnology has recently become a buzzword in several scientific fields, including the area of drug delivery,1 and a variety of nanomedicine opportunities have recently been reviewed.2 The concept of nanoparticles as drug delivery vehicles is not new as reviews on the subject were published nearly 20 years ago.3 That nanoparticles could be selectively targeted by coating with monoclonal antibodies provided an early, ground-breaking proof-of-concept that these materials might one day be effective tools for the diagnosis and treatment of cancers. At their inception, all new technologies

Target

Imagir

Target

Imagir

Delivery

Reporting

Delivery

FIGURE 3.1 Integrated potential applications of nanoparticles as visualized by the National Cancer Institute of the NIH. Nanoparticles, because of their general capacity for multiple modifications as well as their inherent properties, can have multiple functions relevant to targeting cancers for therapeutic and/or diagnostic purposes.

appear to have a plethora of possibilities because limitations have not yet become apparent. Subsequent studies that examine the limits of various applications then provide a menu of feasible applications. This menu can change as new developments of the technology are realized that allow one to address additional applications. This has certainly been the case for nanotechnology applications that involve active targeting to cancers for diagnostic and therapeutic purposes.4

Although nanoparticles have shown tremendous promise in facilitating the targeted delivery of therapeutics and diagnostics to cancers, the composition and size of the particles have inherent physical and chemical properties that can compromise their capability to localize to and/or treat cancers because of non-selective cell and tissue uptake. Therefore, active targeting to cancers using nanoparticles requires consideration of not only unique properties of the cancer that allow for specific targeting but also attention to issues that minimize non-selective delivery to uninvolved regions of the body. Methods to overcome functional barriers that limit uptake of materials or delivery to cancer cells must be also considered. Even with proper consideration of these issues, successful disposition and targeting to cancers is quite a challenge. Certainly, lack of consideration of these issues can dramatically increase the risk of serious negative outcomes, particularly when targeted nanoparticles contain potent cytotoxic agents.

Advantages and disadvantages of specific nanoparticles as well as methods to potentially correct shortcomings of nanoparticle targeting to cancers will be discussed in this chapter. Several of the topics raised in this chapter will also be discussed in much greater depth in other chapters in this text. Specifically, two major strategies of cancer targeting related to nanotechnology opportunities will be addressed: targeting to cancer cells and targeting to tumors. Attention will be paid to similarities as well as differences for these two strategies. Targeting cancer cells and tumors for diagnostic purposes as well as therapy will also be examined. Several applications for nanoparticles have been outlined by the National Cancer Institute (http://nano.cancer.gov) regarding unmet medical needs in the areas of targeting, imaging, delivery, and reporting agents for cancer diagnosis and treatment (Figure 3.1). General cellular responses to and fates of nanoparticles that can affect these potential applications will be discussed as critical aspects of ultimate clinical success.

Clinical success of nanoparticle-based diagnostics and therapeutics requires proper matching of particle characteristics. The characteristics of nanoparticles are critically dependent upon the materials used to prepare the nanoparticle. Nanoparticles can now be readily prepared from a wide range of inorganic and organic materials in a range of sizes from two to several hundred nanometers (nm) in diameter. Put in perspective, human cells are typically 10,000-20,000 nm in diameter. The plasma membrane of these cells is 6 nm in thickness. In most cases, nanoparticles can be generated to have narrow and defined size ranges. Other chapters in this text will focus on the physical and chemical characteristics of nanoparticles made from various materials as well as

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