Targeted in vitro photodynamic therapy via aptamer-labeled, porphyrin-loaded virus capsids

Virus capsids have emerged as multifunctional platform systems for development of bio-derived nanomaterials. In this work we investigate the use of aptamer decorated MS2 bacteriophage capsids, loaded with photosensitizer for targeted photodynamic therapy in vitro. MS2 capsids were loaded with approximately 250 cationic porphyrins through a novel assembly packaging mechanism, followed by exterior decoration of the capsid with a cancer-targeting nucleic acid aptamer via chemical conjugation. The ability of these aptamer-virus-porphyrin constructs to specifically target and eradicate MCF-7 human breast cancer cells upon photoactivation was assessed. Photoinduced cytotoxicity was evaluated via live/dead staining and a metabolic activity assay with MCF-10A cells as a control. Results show that MCF-7 cells incubated with targeted, porphyrin-loaded virus capsids exhibited cell death whereas the MCF-10A cells did not. Furthermore, MCF-7 cells incubated with porphyrin-loaded viruses decorated with a non-targeting aptamer exhibited no observable phototoxicity. Combined, the results presented in this work demonstrate our unique virus-based loading strategy offers a viable approach for efficient targeted delivery of photoactive compounds for site-specific photodynamic cancer therapy using bio-derived nanomaterials.