5H Pyrolo(3,4-b)Pyrazin-5,7-(6H)-dione 6-(N-Chitosanimide nanoparticle) composite nano silver and encapsulation in γ-cyclodextrin: Synthesis, molecular docking, and biological evaluation for thyroid cancer treatment.

BACKGROUND: Thyroid cancer is rapidly increasing worldwide, with some patients facing poor prognosis and recurrence despite current treatments. Chitosan-based nanoparticles have exhibited exciting antitumor efficacy both in vitro and in vivo, which indicates that there is vast scope of clinical application. This study develops a anhydride-modified chitosan and anhydride-modified chitosan‑silver nanoparticles, encapsulated in γ-cyclodextrin to help drug delivery by safe way and enhance thyroid cancer therapy.

METHODS: 5H pyrolo(3,4-b)pyrazin-5,7-(6H)-dione-6-(N-chitosanimide nanoparticle(composite constructed with nano silver (B1) was prepared and the optimized formula was further investigated regarding FT-IR, X-RD, SEM and TEM. Furthermore, it was encapsulated in γ-CD, and an in vivo study was conducted to investigate its anticancer activity. The binding affinities of 2,3-Pyrazinedicarboxylic anhydride to inhibitor of kappa B kinase beta (IKK-β) was demonstrated by molecular docking.

RESULTS: SEM and TEM revealed that Ag NPs were mostly uniformly incorporated into the 5H pyrolo(3,4-b)pyrazin-5,7-(6H)-dione 6-(N-chitosanimide nanoparticle, while FT-IR and X-RD findings verified the formation of 5H pyrolo(3,4-b)pyrazin-5,7-(6H)-dione-6-(N-chitosanimide nanoparticle)/composite constructed with nano silver and encapsulated in γ-CD (B2). γ-CD encapsulation induced a significant enhancement in pyrazine thyroid antitumor activity in xenografic model.

CONCLUSION: B2 could be considered a promising formula for suppression of thyroid cancer by modulating NF-κB signaling pathway, and hence, future studies could be planned to transfer our formula to the clinical field.