Enzyme-conjugated gold nanoparticles for combined enzyme and photothermal therapy of colon cancer cells

摘要

The current investigation introduces an advanced and effective tumor therapeutic RnaGNPs nanobiomedicine composed of gold nanoparticles (GNPs) conjugated with bovine pancreatic ribonuclease (RNase A). The engineered nanobiomedicine was used to overcome the intracellular ribonuclease inhibitors (RIs) as one of the most important obstacles for the clinical applications of RNases in cancer therapy. The RnaGNPs nanobiomedicine was characterized and evaluated for its biological impacts and photothermal effects in the SW-480 colon cancer cells. To determine the efficacy of RnaGNPs combined with the photothermal therapy (PTT), low doses of the near-infrared (NIR) laser irradiation were utilized. The RnaGNPs induced significant cytotoxicity, cell cycle arrest in the sub-G1 phase and a reduction in the G0/G1 and G2/M phases. The RnaGNPs was able to upregulate PTEN, Bax, and caspase 3 and downregulate AKT and Bcl-xL, indicating their key influence in the induction of apoptosis in cancer cells. Mechanistically, the RnaGNPs suppressed the cells' invasion through the downregulation of the extracellular signal-regulated kinases (ERK1/2) pathway. Once combined with PTT, RnaGNPs induced an augmented impact on cancer cells. Based on our findings, the engineered RnaGNP nano-biomedicine is proposed as a treatment modality for the combined enzyme therapy and PTT of colon cancer and other solid tumors.