Radiotherapy is the mainstay for abdomen and pelvis cancers treatment. However, high energy ray would inflict gastrointestinal (GI) system and adversely disrupt the treatment. The anti-oxidative agents provide a potential route for protecting body from radiation-induced injuries. Herein, highly catalytic nanocubes with dislocation structure are developed for treatment of intestinal injury. Structural and catalytic properties show that Mo incorporation can enhance antioxidant activity by dislocation structure in the alloy. In vitro studies showed that PtPdMo improved cell survival by scavenging radiation-induced ROS accumulation. Furthermore, after animals were exposed to lethal dose of radiation, the survival was increased by 50% with the PtPdMo i.p. treatment. Radioprotection mechanism revealed that PtPdMo alleviated the oxidative stress in multi-organs especially the small intestine by inhibiting intestinal epithelium apoptosis, reducing DNA strands breaks and enhancing repairing ability. In addition, PtPdMo protected hematopoietic system by improving the number of bone marrow and peripheral blood cells.

Antibody directed enzyme prodrug therapy (ADEPT) utilizing β-lactamase is a promising treatment strategy to enhance the therapeutic effect and safety of cytotoxic agents. In this method, a conjugate (antibody-β-lactamase fusion protein) is employed to precisely activate nontoxic cephalosporin prodrugs at the tumor site. A major obstacle to the clinical translation of this method, however, is the low catalytic activity and high immunogenicity of the wild-type enzymes. To overcome this challenge, we fused a cyclic decapeptide (RGD4C) targeting to the integrin with a β-lactamase variant with reduced immunogenicity which retains acceptable catalytic activity for prodrug hydrolysis. Here, we made a further investigation on its targeting effect and pharmacokinetic properties, the results demonstrated that the fusion protein retains a targeting effect on integrin positive cells and has acceptable pharmacokinetic characteristics, which benefits its use in ADEPT.