Peripheral Tailoring of Pentacene: Developing Next-Generation Organic Sonosensitizers for Cancer Sonodynamic Therapy

Sonodynamic therapy (SDT) is an innovative, non-invasive, and effective method for cancer treatment. However, exploring sonosensi-tizers with high sonosensitivity and biosafety remains a significant challenge. Recent investigations have demonstrated that the excel-lent delocalized π-electron conjugation system and narrow HOMO-LUMO gap characteristic of acenes endow them with intrinsic son-oactivity, providing a 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 excel-lent 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.