Quercetin Encapsulated Biodegradable Plasmonic Nanoparticles for Photothermal Therapy of Hepatocellular Carcinoma Cells.

Abstract

Photothermal therapy (PTT) is emerging as an effective treatment modality for cancer due to its noninvasive nature. However, the pro-inflammatory necrotic cell death during PTT limits its successful clinical application. Here, we have developed quercetin (QE)-loaded biodegradable plasmonic nanoparticles that can specifically induce apoptosis in cancer cells after PTT. We have synthesized gold-coated liposome (LiposAu) and QE-loaded gold-coated liposome (QE-LiposAu) nanoparticles by in situ reduction of chloroauric acid with ascorbic acid in the presence of bare liposomes (Lipos) or QE-loaded liposomes (QE-Lipos), respectively. The gold coating was confirmed by transmission electron microscopic analysis, dynamic light scattering, and ζ potential measurements. LiposAu and QE-LiposAu nanoparticles showed a similar level of temperature rise upon 750 nm near-infrared (NIR) laser (650 mW, 3 W cm-2) irradiation. The photothermal conversion efficiency of QE-LiposAu nanoparticles was determined to be ∼75%. The efficacy of PTT was found to be dependent on the internalization efficiency of LiposAu nanoparticles in cancer cells. Importantly, QE-LiposAu nanoparticles showed increased PTT efficacy over LiposAu nanoparticles in hepatocellular carcinoma cells (Huh-7). Moreover, QE-LiposAu nanoparticles induced apoptosis-mediated cell death after the PTT, and the extent of apoptosis was significantly higher than the LiposAu nanoparticles in Huh-7 cells. Further, QE-LiposAu nanoparticles-mediated PTT depolymerized microtubules network, suppressed Hsp70 expression, and caused DNA damage. QE-LiposAu nanoparticles were also found to be hemocompatible. The results together suggested that biodegradable QE-LiposAu nanoparticles are promising photothermal agents for cancer therapy.