A dual-targeting ruthenium nanodrug that inhibits primary tumor growth and lung metastasis via the PARP/ATM pathway

Background Many studies have found that ruthenium complexes possess unique biochemical characteristics and inhibit tumor growth or metastasis. Results Here, we report the novel dual-targeting ruthenium candidate 2b, which has both antitumor and antimetastatic properties and targets tumor sites through the enhanced permeability and retention (EPR) effect and transferrin/transferrin receptor (TF/TFR) interaction. The candidate 2b is composed of ruthenium-complexed carboline acid and four chloride ions. In vitro, 2b triggered DNA cleavage and thus blocked cell cycle progression and induced apoptosis via the PARP/ATM pathway. In vivo,2b inhibited not only Lewis lung cancer (LLC) tumor growth but also lung metastasis. We detected apoptosis and decreased CD31 expression in tumor tissues, and ruthenium accumulated in the primary tumor tissue of C57BL/6 mice implanted with LLC cells. Conclusions Thus, we conclude that 2b targets tumors, inhibits tumor growth and prevents lung metastasis.

Automated summary

In this study, a novel dual-targeting ruthenium candidate 2b was reported to possess anti-tumor and anti-metastatic properties, targeting tumor sites through the EPR effect and TF/TFR interaction. In vitro and in vivo experiments demonstrated that 2b inhibited tumor growth and prevented lung metastasis effectively.