κ-carrageenan - Gelatin hydrogel embedding carvacrol loaded gold nanobipyramids for treating prostate cancer via fractionated photothermal-chemotherapy.

Conventional treatment of prostate cancer need more specificity, and higher efficiency. The present work is the first attempt to utilize hydrogel-loaded carvacrol-based chemotherapy with fractionated photothermal therapy (F-PTT) using a 635 nm laser for its treatment. Gold nanobipyramids (AuNBPs) were used as drug carrier and photosensitizer. A marine-derived hydrogel (AuNBP-HG) was fabricated and physicochemically characterized. A 635 nm NIR light was used for the fractionated PTT in three cycles of treatment on different days at varying power densities for 5 min. The efficiency of single and dual treatments was experimented in vitro and in vivo. The results showed that the dual therapy imparted a better effect than monotherapy. The AuNBP-CVL synthesized was nearly 50 nm and efficiently loaded within AuNBP-HG, displaying thermal responsiveness, a good sol-gel transition, a controlled drug release rate, and high stability. In vitro evaluation demonstrated that the F-PTT evinced stability during temperature rise without damaging healthy surrounding tissue. In vivo study revealed that a stable temperature rise up to 60 °C by the 635 nm NIR light due to photosensitization of AuNBP and sustained CVL release from AuNBP-HG into the tumor microenvironment exhibited successful thermal ablation of the cancer cells. Histological analysis confirmed that the uniform suspension of AuNBP within cancer tissues might have enhanced tumor cell lysis during the dual therapy. Western blot analysis exhibited that the cellular death could result from the upregulation of pJNK and p53 protein. In conclusion, the current study illustrated that dual therapy could be a feasible alternative to non-target specific and invasive traditional therapies against prostate cancer.