Abstract
The advantages of targeted therapy have motivated many efforts to find distinguishing features between the molecular cell surface landscapes of diseased and normal cells. Typically, the features have been proteins, lipids or carbohydrates, but other approaches are emerging. In this discussion, we examine the use of cell surface acidity as a feature that can be exploited by using pH-sensitive peptide folding to target agents to diseased cell surfaces or cytoplasms.
Highlights
Targeting therapeutic agents to diseased tissues can significantly enhance their efficacy by reducing side effects
A fluorescent agent has been developed using ICG, an indocyanine near infrared (NIR) fluorescent dye widely used for circulatory imaging (Desmettre et al, 2000; Alander et al, 2012)
Exogenous antibodies or antibody drug conjugates (ADCs) could be administrated to target specific antigens delivered to tumor cells by pH (Low) Insertion Peptides (pHLIPs)
Summary
Targeting therapeutic agents to diseased tissues can significantly enhance their efficacy by reducing side effects. Successful molecular targeting approaches have usually been based on distinguishing the cells in a diseased tissue from those in a healthy tissue by exploiting surface features. The advantages of targeted therapy have motivated searches for distinguishing features between the molecular cell surface landscapes of diseased and normal cells. In this discussion we emphasize an alternative for targeting: cell surface acidity. In addition to the targeting of biomarkers or membrane properties, cells within diseased tissues have pronounced surface acidity resulting from their metabolism. Such acidity can be targeted by pH-triggered membrane-associated peptide folding, which is the subject of this review
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