Photosensitizers Dispersed on Nanosized Triterpenoid Matrix with Deaggregation-Enhanced Singlet Oxygen Production

Aggregation-caused quenching (ACQ) effects of photosensitizers severely cut down the generation of quantum yield of singlet oxygen (¹O₂) for effective photodynamic therapy (PDT). Herein, we accomplish a deaggregation-enhanced ¹O₂ production strategy by the noncovalent coordination of a clinically applied triterpenoid oleanolic acid (OA) and hematoporphyrin (Hp) via one-step self-assembly, forming a nanosensitizer OH, in which Hp is interspersed on the surface of the OA matrix in a face-to-face manner. The scattered arrangement of Hp held by the OA matrix decreases the π–π aggregation in Hp, leading to a 3.7-fold boost in the intracellular ¹O₂ yield and high phototoxicity in vitro and in vivo. Moreover, the biologically active OA enables OH to display excellent cellular uptake efficiency (increase by 36-fold), deep tumor penetration, and synergistic antitumor outcome at a low dose. Thus, this simple strategy paves the way for the green development of efficient photosensitizers.