期刊
ADVANCED MATERIALS
卷 31, 期 46, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201905091
关键词
cancer therapy; metastasis; organic nanoparticles; photoactivation; prodrugs
类别
资金
- Nanyang Technological University [NTU-SUG: M4081627.120]
- Singapore Ministry of Education, Academic Research Fund Tier 1 [2017-T1-002-134-RG147/17]
- Singapore Ministry of Education, Academic Research Fund Tier 2 [MOE2016-T2-1-098]
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 (O-1(2)) cleavable linker. Such a designed molecular structure not only enables generation of O-1(2) 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.
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