Biodegradable Radiofrequency Responsive Nanoparticles for Augmented Thermal Ablation Combined with Triggered Drug Release in Liver Tumors

Vijay Harish Somasundaram, Rashmi Pillai, Giridharan Malarvizhi, Anusha Ashokan, Siddaramana Gowd, Reshmi Peethambaran, Shanmugasundaram Palaniswamy, A. K K Unni, Shantikumar Nair*, Manzoor Koyakutty

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Radiofrequency ablation (RFA) and doxorubicin (Dox) chemotherapy are separately approved for liver cancer therapy; however, both have limited success in the clinic due to suboptimal/nonuniform heating and systemic side effects, respectively. Here, we report a biodegradable nanoparticle (NP) system showing excellent RF hyperthermic response together with the ability to locally deliver Dox in the liver under RF trigger and control. The nanosystem was prepared by doping a clinically permissible dose (∼4.3 wt %, 0.03 ppm) of stannous ions in alginate nanoparticles (∼100 nm) coloaded with Dox at ∼13.4 wt % concentration and surface conjugated with galactose for targeting asialo-glycoprotein receptors in liver tumors. Targeted NP-uptake and increased cytotoxicity when combined with RF exposure was demonstrated in HEPG2 liver cancer cells. Following in vitro (chicken liver phantom) demonstration of locally augmented RF thermal response, in vivo scintigraphic imaging of 99Tc-labeled NPs was performed to optimize liver localization in Sprague-Dawley (SD) rats. RF ablation was performed in vivo using a cooled-tip probe, and uniformly enhanced (∼44%) thermal ablation was demonstrated with magnetic resonance imaging along with RF-controlled Dox release. In orthotopic rat liver tumor models, real-time infrared imaging revealed significantly higher (∼20 °C) RF thermal response at the tumor site, resulting in uniform augmented ablation (∼80%) even at a low RF power exposure of 15 W for just 1 min duration. Being a clinically acceptable, biodegradable material, alginate nanoparticles hold strong translational potential for augmented RF hyperthermia combined with triggered drug release.

Original languageEnglish
Pages (from-to)768-779
Number of pages12
JournalACS Biomaterials Science and Engineering
Volume2
Issue number5
DOIs
Publication statusPublished - 9 May 2016
Externally publishedYes

Keywords

  • biodegradable nanoparticles
  • doxorubicin
  • HCC
  • radiofrequency responsive nanoparticle
  • RF-triggered drug release

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