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 (SPN_B) is developed that can inhibit intracellular protein synthesis upon near-infrared (NIR) photoactivation to synergize with photodynamic therapy (PDT) for metastasis-inhibited cancer therapy. SPN_B 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, SPN_B exerts a synergistic action to afford an enhanced therapeutic efficacy in tumor ablation. More importantly, SPN_B-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.