Urgency in finding a suitable therapy in tumor hypoxia strives to develop hypoxia-targeted activatable theranostic. A strategic theranostic prodrug (Azo-M) has been synthesized. Its azo-linker scission under the hypoxia condition has released an near-infrared (NIR)-reporter to determine the extent of chemotherapeutic (melphalan analogue) activation. Under an artificial hypoxia condition, a large shift from 520 to 590 nm in UV absorption was observed in Azo-M. Alongside, the emission maxima had appeared at 625 nm under the said condition. The Azo-M post-incubated HeLa cells have shown upregulation of various apoptotic factors under oxygen deprivation (3%) condition. Azo-M has shown antiproliferative activity under hypoxia conditions in various cancer cells. An ex-vivo biodistribution study indicated that theranostic Azo-M only activated in tumor tissue and to some extent in the liver. The therapeutic activity study in vivo indicated that Azo-M effectively reduced the tumor size and volume (about 2-fold) without the change of bodyweight of mice. The theranostic Azo-M can be a cornerstone to suppress tumor hypoxia and tracking its extent of suppression.
Keywords: NIR-theranostic probe; antiproliferative activity; hypoxia-inducible factor; hypoxia-sensitive; tumor suppressor.