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摘要
Therapy-induced DNA damage is the most common strategyto inhibittumor cell proliferation, but the therapeutic efficacy is limitedby DNA repair machinery. Carrier-free nanoproteolysis targeting chimeras(PROTACs), designed as SDNpros, have been developed to enhance photodynamictherapy (PDT) by blocking the DNA damage repair pathway through BRD4degradation. Specifically, SDNpros are constructed through noncovalentinteractions between the photosensitizer of chlorine e6 (Ce6) andPROTACs of BRD4 degrader (dBET57) via self-assembly. SDNpro has favorabledispersibility and a uniform nanosize distribution without drug excipients.Upon light irradiation, SDNpro produces abundant reactive oxygen species(ROS) to induce DNA oxidative damage. Meanwhile, the DNA repair pathwaywould be interrupted by the concurrent degradation of BRD4, whichcould intensify the oxidative DNA damage and elevate PDT efficiency.Beneficially, SDNpro suppresses tumor growth and avoids systemic sideeffects, providing a promising strategy to promote the clinical translationof PROTACs for tumor treatment.
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单位5; 广州医学院; 南方医科大学
