pH-triggered small molecule theranostic nanodrug mediates selective tumor CT imaging and chemotherapy

Theranostic nanomedicines have garnered significant attention in cancer management. However, they have yet to achieve clinical transformation due to a lack of precise structure and tumor selectivity. Herein, this work highlights the successful development of a pH-triggered dynamic small molecule nanodrug for targeted tumor theranostics, constructed through self-assembly of orthoester-linked 2,3,5-iodobenzoic acid dimers and doxorubicin by the O/W emulsion solvent evaporation method. The nanodrug exhibits favorable characteristics such as simple preparation, well-defined structure, and high drug loading capacity. Furthermore, it demonstrates superior dynamic alterations in physicochemical properties such as small-to-large size transition, progressive amino protonation and selective drug release across physiological pH (7.4) to tumoral extracellular pH (6.5) and intracellular pH (5.0) levels. These features result in long-term storage stability and circulation longevity while enhancing tumor accumulation by intravenous administration for targeted CT imaging along with significant inhibition of tumor growth. Thus, the pH-triggered small molecule dynamic theranostic nanodrug mediates selective tumor CT imaging and chemotherapy, significantly advancing its potential for clinical application.