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.

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.

Real-time live cell imaging and quantification of biothiols dynamics are important for understanding the pathophysiological process. However, it is still challenging in the design and synthesis of rational probes that...