Nanoformulations mediated metastasis brake in cancer therapy via photodynamic-enhanced ferroptosis and regional inflammation management

Tumor therapy should not only pursue the efficient killing of tumor tissues, but also consider the restriction on metastasis of residual tumor cells after local tumor destruction, because metastasis would bring irreparable consequences. In view of this, a combinational drug delivery system was constructed to enhance tumor killing activity and inhibit metastasis through rational synergy of antitumor and anti-inflammatory functions of small molecule drugs, photosensitizer Ce6 and sulfasalazine (SAS). The nanoformulations can activate programmed ferroptosis in tumor cells assisted by photodynamic therapy, leading to accurate tumor killing enhancement. On the other hand, besides participating in ferroptosis cascade, SAS suppressed the migration behavior of surviving tumor cells after treatment stimulation via inhibiting proinflammatory signaling pathway nuclear-factor kappa B (NF-κB), which was confirmed in vitro and in vivo. Together, this work provides an excellent paradigm of combined medication, and inspires new thinking on oncotherapy and inflammatory response.