Abstract

As a critical regulator of tumor proliferation, the mTOR pathway could enhance the growth, metabolism, and metastasis of numerous malignant tumors, which would weaken the antitumor effect of photodynamic therapy (PDT). Herein, we conceived a pure-drug-assembled nanomedicine (named CeBez) only comprised of the photosensitizer of chlorine e6 (Ce6) and Bez235 (Bez) for chemo-/photodynamic therapy. Bez, a potent inhibitor of the PI3K/AKT/mTOR pathway targeting both PI3K and mTOR, could specifically downregulate mTOR to achieve chemotherapy. CeBez exhibited excellent dispersibility and a favorable stability in water as a result of firm interactions of hydrophobic and electrostatic forces between Bez and Ce6. Particularly, CeBez was capable of passively targeting the tumor site via enhanced permeability and retention (EPR) effects for effective tumor cell internalization after intravenous administration. Under light irradiation, Ce6-mediated PDT could induce cell apoptosis by causing massive singlet oxygen (1O2) generation. Moreover, Bez could not only downregulate mTOR for chemotherapy but also enhance PDT. This self-assembled nanomedicine provided a synergistic effect by efficient chemotherapy and PDT for malignant tumor treatment.