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.
Keywords: aggregation; hematoporphyrin; nanosensitizer; photodynamic activity; triterpenoid.