CO/light dual-activatable Ru(II)-conjugated oligomer agent for lysosome-targeted multimodal cancer therapeutics
Stimuli-activatable and subcellular organelles-targeted agents with multimodal therapeutics is urgently desired for highly precise and effective cancer treatment. Herein, a CO/light dual-activatable Ru(II)-oligo-(thiophene ethynylene) (Ru-OTE) for lysosome-targeted cancer therapy is reported. Ru-OTE is prepared through coordination-driven self-assembly of a cationic conjugated oligomer (OTE-BN) ligand and a Ru(II) center. Upon the dual-triggering of internal gaseous signaling molecule CO and external light, Ru-OTE undergoes ligand substitution and releases OTE-BN followed by the dramatical fluorescence recovery, which could be used for monitoring drug delivery and imaging guided anticancer treatments. The released OTE-BN selectively accumulates in lysosomes, physically breaking their integrity. Then, the generated cytotoxic singlet oxygen (1O2) can cause severe lysosome damage, thus leading to cancer cell death through photodynamic therapy (PDT). Meanwhile, the release of Ru(II) core also suppresses cancer cell growth as an anticancer metal drug. The significant anticancer effect is realized by the multimodal therapeutics of physical disruption/PDT/chemotherapy. Importantly, Ru-OTE can be directly photo-activated by two-photon laser (800 nm) for efficient drug release and near infrared PDT. Furthermore, Ru-OTE with light irradiation inhibits tumor growth in the MDA-MB-231 breast tumor model with negligible side effects. This study demonstrates that the development of activatable Ru(II)-conjugated oligomer potential drug provides a new strategy for effective subcellular organelles-targeted multimodal cancer therapeutics.