Small solutions for big problems: the application of nanoparticles to brain tumor diagnosis and therapy.

Why NaNoparticles? One of the key reasons that nanoparticles have promise in the treatment of cancer is that they can be targeted to tumors through antigen-dependent (specific) or antigen-independent (nonspecific) mechanisms. Specific targeting relies on the interaction of antigens on the surface of nanoparticles with tumor cell receptors. A variety of molecules including peptides (arginine– glycine–aspartic acid,1 F3,2 and chlorotoxin3), cytokines (interleukin-134), drugs (methotrexate5), antibodies (anti-epithelial growth factor antibodies6), and ferromagnetic agents7 have been proposed as targeting modalities. Multiple targeting molecules can be added to the surface of nanoparticles to tailor targeting of brain tumors through a concept referred to as “surface-mediated multivalent affinity effects.”1 Nonspecific targeting relies on the preferential extravasation of nanoparticles into the brain through vascular access provided by blood–brain barrier (BBB) breakdown, which occurs in many brain tumors. Other small molecules can also cross BBB defects. However, unlike small molecules that diffuse freely into and out of a tumor, nanoparticles accumulate within a tumor because of the enhanced permeability and retention effect. The effect accounts for the observation that nanoparticles are retained within tumor tissue after serum levels decline. The enhanced permeability and retention effect results from active angiogenesis, the expression of vascular mediators of extravasation, and altered vascular architecture.8 In addition to their potential for targeting, the physicochemical properties of nanoparticles make them ideal devices for the delivery of compounds to brain tumors. Molecules such as contrast agents or drugs can be loaded into the core of a nanoparticle or applied as a coating to its surface. The process of a single nanoparticle carrying a large number of drug molecules or ions is referred to as “nanoparticle amplification”1 and explains the concept of nanoparticles as delivery devices. In addition, molecules with different functions can be incorporated into a nanoparticle to create multifunctional nanoparticles (Figure 1). The size and chemical composition of a nanoparticle can be altered to control the efficiency of small-molecule loading. The performance of nanoparticles in biological systems suggests that by isolating their payload from the surrounding environment, they may reduce the systemic toxicity associated with conventional chemotherapeutic agents. Moreover, nanoparticles create a barrier to degradation of their payload by preventing contact with plasma enzymes.