Understanding the interplay between pH and charges for theranostic nanomaterials

Nanotechnology has emerged as a highly promising platform for theranostics, offering dual capabilities in targeted imaging and therapy. Interactions between the nanomaterial and biological components determine the in vivo fate of these materials which makes the control of their surface properties of utmost importance. Nanoparticles with neutral or negative surface charge have a longer circulation time while positively charged nanoparticles have higher affinity to cells and better cellular uptake. This trade-off presents a key challenge in optimizing surface charge for theranostic applications. A sophisticated solution is an on-demand switch of surface charge, enabled by leveraging the distinct pH conditions at the target site. In this review, we explore the intricate relationship between pH and charge modulation, summarizing recent advances in pH-induced charge-switchable nanomaterials for theranostics over the past five years. Additionally, we discuss how these innovations enhance targeted drug delivery and imaging contrast and provide perspectives on future directions for this transformative field.