Near‐Infrared Photoactivatable Semiconducting Polymer Nanoblockaders for Metastasis‐Inhibited Combination Cancer Therapy

Inhibition of protein biosynthesis is a promising strategy to develop new therapeutic modalities for cancers; however, noninvasive precise regulation of this cellular event in living systems has been rarely reported. In this study, a semiconducting polymer nanoblockader (SPNB) is developed that can inhibit intracellular protein synthesis upon near‐infrared (NIR) photoactivation to synergize with photodynamic therapy (PDT) for metastasis‐inhibited cancer therapy. SPNB is self‐assembled from an amphiphilic semiconducting polymer which is grafted with poly(ethylene glycol) conjugated with a protein biosynthesis blockader through a singlet oxygen (1O2) cleavable linker. Such a designed molecular structure not only enables generation of 1O2 under NIR photoirradiation for PDT, but also permits photoactivation of blockaders to terminate protein translation. Thereby, SPNB exerts a synergistic action to afford an enhanced therapeutic efficacy in tumor ablation. More importantly, SPNB‐mediated photoactivation of protein synthesis inhibition precisely and remotely downregulates the expression levels of metastasis‐related proteins in tumor tissues, eventually contributing to the complete inhibition of lung metastasis. This study thus proposes a photoactivatable protherapeutic design for metastasis‐inhibited cancer therapy. A near‐infrared (NIR) photoactivatable semiconducting polymer nanoblockader is developed for metastasis‐inhibited combination cancer therapy. Such a nanoblockader can precisely inhibit intracellular protein synthesis upon NIR photoactivation to synergize with photodynamic therapy, affording an enhanced therapeutic efficiency in ablating tumors and inhibiting lung metastasis in a mouse model via downregulating the expressions of metastasis‐related proteins.