Multifunctional nanogel based on carboxymethyl cellulose interfering with cellular redox homeostasis enhances phycocyanobilin photodynamic therapy.

The redox homeostasis defense mechanism of tumor cells is one of the prime reasons for the unsatisfactory effect of photodynamic therapy (PDT). So far, little attention has been paid to this obstacle. In this work, we reported a synthesizing simple yet versatile nanogel (BCPS), synthesized by cystamine dihydrochloride functionalized sodium carboxymethylcellulose (CMC-SS), bovine serum albumin, and Phycocyanobilin self-assembly. The BCPS reduced the levels of glutathione molecules by reacting with glutathione, thereby interfering with intracellular redox homeostasis and enhancing the sensitivity of tumor cells to PDT. The BCPS was shown to possess excellent serum stability, high blood compatibility, low toxic side effects, and higher reactive oxygen species (ROS) utilization. After irradiation, the BCPS could significantly increase intracellular ROS level by approximately 1.6-fold and decrease the IC50 to HeLa cells by approximately 1.5-fold, compared to the pre-functional drugs BCP. This proposed strategy, based on increasing the utilization rate of ROS in tumor cells is promising for application potentials in tumor therapy.