Abstract
Sonodynamic therapy (SDT) is an innovative, non-invasive, and effective method for cancer treatment. However, exploring sonosensitizers with high sonosensitivity and biosafety remains a significant challenge. Recent investigations have demonstrated that the excellent delocalized π-electron conjugation system and narrow HOMO-LUMO gap characteristic of acenes endow them with intrinsic sonoactivity, providing an opportunity for advancing novel sonosensitizers. Herein, two pentacene derivatives, 4Br-PEN and 4Br-CN-PEN, were successfully synthesized through site-specific peripheral tailoring of the pentacene backbone with bromine atoms and cyano groups. Both in vitro and in vivo therapeutic outcomes demonstrated that the synthesized compounds could generate singlet oxygen ((1)O(2)) under ultrasound irradiation, effectively eradicating cancer cells while exhibiting significant anti-proliferative effects and excellent biocompatibility. Notably, because of the synergistic inductive and conjugative effects of the cyano group, 4Br-CN-PEN exhibited superior sonodynamic activity to 4Br-PEN. These findings collectively suggest that pentacene derivatives hold promising potential as highly effective and safe sonosensitizers for SDT applications.