Enhanced tumor targeting with near-infrared light-activated indocyanine green encapsulated in covalent organic framework for combined photodynamic therapy (PDT) and photothermal therapy (PTT)

Covalent organic framework (COF), a new emerging class of crystalline porous polymeric networks with reversible covalent bonds are a better smart material in Nano medicine in this regard. 1,3,5-Triformylbenzene (TFB) and 2,5-Bis(methylsulfonyl)-1,4-diaminobenzene (BMSDAB) are used to develop a uniform shaped cova-lent organic framework at room temperature (RT-USCOF). In order to achieve the PTT and PDT effect in RT-USCOF, near infrared photosensitizer, photothermal and fluorescence agent, indocyanine green (ICG) was encapsulated. Moreover, enhanced loading content of ICG in I RT-USCOF to produce II RT-USCOF followed by stabilize with hyaluronic acid designed in order to reduce drug leakage and increase carrier stability. The II RT-USCOF-HA exhibits an increased encapsulation efficiency of 57.75% and a drug loading capacity of 53.59%. The developed system shows an 80% ICG release upon exposure to NIR 808-laser in acidic pH relative to the one without light irradiation proved the effective structural changes under light cause drug release. The newly developed II RT-USCOF-HA shows excellent biocompatibility against NIH 3T3 cell lines and CT2A cell lines under dark. Whereas, upon irradiation with NIR 808 nm laser, the system kills more than 70% of the cells and cellular uptake studies also proved the same. Finally, flow cytometry analysis confirmed, the II-RT-USCOF-HA treated with CT2A cell lines shows an early apoptosis cell population of 1.95%, a late apoptosis rate of 1.24% and a necrotic cell death of 4.77%, which are significantly greater than the free ICG treated groups. The singlet oxygen production followed by thermal ablation of tumor cells by the developed system further demonstrates its efficacy as a PDT/PTT probe.