Metabolic Environment

Solid tumors typically grow at such a rapid pace that vascular function fails to keep pace with local metabolic requirements. This situation, leading to reduced oxygen tension and a depressed pH as a result of a lack of waste acid clearance, is associated with the onset of necrotic cores of large tumors. A number of studies have shown that cancer cells become adapted to successful growth in these difficult conditions, providing unique characteristics that might be exploited for tumor targeting. For example, nanoparticles will accumulate at inflammation sites along the bowel when administered orally.108,109 Because these inflammatory sites are typically associated with a slightly acidic environment, a similar targeting strategy may be possible for tumors where the pH has also been depressed. Nanoparticles targeted to cancer cells might also be modified at low oxygen tension to either release or activate a payload. Frequently, cancer cells rely more on glycolysis than oxidative metabolism for energy production. This finding is consistent with the reduced oxygen tension of poorly perfused tumors. These conditions would result in the release of acidic glycolytic end-products that are not effectively cleared by the sluggish blood flow through tumor vascular beds. Therefore, targeting that takes advantage of a slightly depressed local pH that might be found in some tumors could be an attractive design strategy.

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