C=C Bond Oxidative Cleavage of BODIPY Photocages by Visible Light.

Photocages for protection and the controlled release of bioactive compounds have been widely investigated. However, the vast majority of these photocages employ the cleavage of single bonds and high-energy ultraviolet light. The construction of a photoactivation system that uses visible light to cleave unsaturated bonds still remains a challenge. Herein, we report a regioselective oxidative cleavage of C=C bonds from a boron-dipyrrolemethene (BODIPY)-based photocage by illumination at 630 nm, resulting in a free aldehyde and a thiol fluorescent probe. This strategy was demonstrated in live HeLa cells, and the generated α-formyl-BODIPY allowed real-time monitoring of aldehyde release in the cells. In particular, it is shown that a mannose-functionalized photocage can target HepG2 cells.

Controlled Intracellular Polymerization for Cancer Treatment.

Numerous prodrugs have been developed and used for cancer treatments to reduce side effects and promote efficacy. In this work, we have developed a new photoactivatable prodrug system based on intracellular photoinduced electron transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization. This unique polymerization process provided a platform for the synthesis of structure-predictable polymers with well-defined structures in living cells. The intracellularly generated poly(N,N-dimethylacrylamide)s were found to induce cell cycle arrest, apoptosis, and necroptosis, inhibit cell proliferation, and reduce cancer cell motilities. This polymerization-based "prodrug" system efficiently inhibits tumor growth and metastasis both in vitro and in vivo and will promote the development of targeted and directed cancer chemotherapy.

BODIPY based realtime, reversible and targeted fluorescent probes for biothiol imaging in living cells.

Real-time live cell imaging and quantification of biothiol dynamics are important for understanding pathophysiological processes. However, the design and synthesis of rational probes that have reversible and real-time capabilities is still challenging. In this work, we have prepared boron-dipyrrolemethene (BODIPY) based fluorescent molecules as ratiometric probes that allow the real-time biothiol dynamics to be observed in living cells. The Michael reaction between α-formyl-BODIPY (BOD-JQ) and GSH exhibited a reversible fluorogenic mechanism with fluorescent emission shifting from 592 nm to 544 nm with t1/2 = 16 ms. In particular, we showed that the probes with targeting agents are capable of detecting biothiols in mitochondria and the endoplasmic reticulum (ER) with high temporal resolution.