Near-infrared-triggered Dibenzo[a,c][1,2,5]thiadiazolo[3,4-i]phenazine heterocyclic derivatives for type-I photodynamic and photothermal therapy against human nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) remains endemic in southern China. The general therapeutic consensus is to treat the disease with radiotherapy alone or together with concurrent chemotherapy. But the treatment outcome of NPC remains disappointing with bad prognoses, low overall survival rate and severe side effects. Phototherapy can be a promising approach for treating NPC due to its excellent spatiotemporal selectivity, negligible drug resistance and minimal invasiveness. In this work, two photosensitizers (DTP-Ph and DTP-Et) with similar donor-acceptor structure were designed and constructed for the treatment of NPC. Remarkably, DTP-Ph and DTP-Et show different photo-physicochemical properties as well as mechanisms of phototherapeutic actions, especially DTP-Ph, which exhibits synergistic type-I photodynamic therapy (PDT) and photothermal therapy (PTT) effect under near-infrared (NIR) activation. DTP-Et and DTP-Ph were further encapsulated with F127 to obtain nanoparticles with good water solubility. In intro and in vivo phototherapy evaluations of DTP-Ph NPs display promising phototherapeutic activity with low IC50 value and good tumor growth inhibition (TGI) against human nasopharyngeal carcinoma cell line CNE2 and tumor-bearing xenograft model.