Improving cancer chemotherapy through photothermally triggered drug release from poly(N-isopropylacrylamide-co-acrylic acid)/Prussian blue hydrogel

Abstract

Recently, microgel-based drug delivery systems have received great attention. However, these systems face various challenges such as low drug loading, leakage, rapid drug elimination by the bloodstream, and low efficacy against tumors. To overcome these limitations, we fabricated a near-infrared (NIR)-responsive poly(N-isopropylacrylamide-co-acrylic acid)/Prussian blue microgel (PNA@PB). The microgel featured improved stability and higher loading of Prussian blue (PB), achieved by chemically linking it to the polymer. For cancer therapy, the microgel was loaded with the model drug doxorubicin (DOX) to obtain PNA@PB@DOX, resulting in a high loading capacity of 26% and encapsulation efficiency of 51%. Upon exposure to 808 nm NIR laser light, the photothermal PB in PNA@PB@DOX raised the temperature above the lower critical solution temperature of the microgel, causing the microgel to shrink and release the drug by 36%. The NIR-triggered drug release by PNA@PB@DOX resulted in improved photothermal/chemotherapy performance, both in vitro and in vivo experiments using A549 lung cancer cells, compared with PNA@PB. The combination of photothermal therapy from PB and photothermal shrinkage-induced chemotherapy from PNA was found to be highly effective in killing cancer cells.