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.

NIR-I fluorescence imaging tumorous methylglyoxal by an activatable nanoprobe based on peptide nanotubes by FRET process.

Methylglyoxal (MGO), a glycolysis metabolite with high reactivity, can nonenzymatically modify proteins, lipids and nucleic acids etc., and it is closely related to the development of tumors. The accurate detection and high-performance optical imaging of MGO from deep tumor issues is of great significance for understanding their roles in tumor initiation and progression. Herein, we have presented a nanoprobe D/I-PNTs with emission in the first near infrared (NIR-I) region by employing a fluorescence resonance energy transfer (FRET) process between a far-red emission MGO probe and IR783 based on peptide nanotubes. The nanoplatform extended the emission range of MGO probe through FRET process and avoided complex molecular design and synthesis. The biocompatible peptide nanotubes improved the water solubility of MGO probe. D/I-PNTs was sensitive to MGO with a detection limit of 272 nM and enabled high-resolution NIR-I fluorescence imaging of MGO induced by glyoxalase I (GLO1) inhibitor in tumor with higher penetration depth (∼4 mm) than that in visible (Vis) region (∼3 mm). Most importantly, the FRET process based on the structure characteristics of peptide nanotubes can be a universal approach to realize the extension of emission wavelength and ratio detection of target analytes, which will be a promising strategy for bioimaging in deep tissue with high contrast.