Construction of a multifunctional peptide nanoplatform for nitric oxide release and monitoring and its application in tumor-bearing mice

As a “star molecule”, nitric oxide (NO) either promotes or inhibits many physiological processes depending on its concentration. The in situ generation and monitoring of therapeutic gas molecules has been a problem that many researchers have been working to address due to the stochastic nature of gas molecule movement. There are still relatively few studies using short peptides as NO storage systems, and there are still challenges in monitoring NO release in situ with real-time imaging over long periods of time. In this work, a morphologically transformable NO release, diagnosis and treatment integrated multifunctional nanoplatform was fabricated. A new NO-activated probe (DPBTD) with emission in the first near infrared (NIR-I) region was encapsulated into the hydrophobic domains of Ac-KLVFFAL-NH₂ peptide derivatives as a biosensor for NO release. Peptide scaffolds were endowed with the capacity of controlled NO release by the introduction of NO donor (organic nitrates). Interestingly, morphology of the nanoplatform could be transformed from one-dimensional (1D) nanowires to two-dimensional (2D) nanosheets via nanorods transition state under tip sonication, which was allowed for better cell uptake. Eventually, this nanocarrier was used for stimuli-responsive NO release, real-time imaging and treatment in tumor tissues of 4T1 tumor-bearing mice. This strategy expands the application potential of peptide-based nanomaterials and provides ideas for monitoring the progress of gas-mediated cancer therapy.