Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy

• Published in: PloS one 2014-08, Vol.9 (8), p.e102727
• Main Authors: Moussa, Marwan, Goldberg, S Nahum, Kumar, Gaurav, Sawant, Rupa R, Levchenko, Tatyana, Torchilin, Vladimir P, Ahmed, Muneeb
• Format: Article
• Language: English
• Subjects: Ablation; Ablation (Surgery); Ablative materials; Animals; Anthracyclines; Antibiotics, Antineoplastic - administration & dosage; Beads; Biotechnology; Carriers; Catheter Ablation; Cell cycle; Chemoradiotherapy; Chemotherapy; Coagulation; Doxorubicin; Doxorubicin - administration & dosage; Drug delivery; Drug delivery systems; Female; Fever; Fluorescence; Heat; Heat shock proteins; Hsp70 protein; Hyperthermia; Hypoxia; Laboratories; Liposomes; Liver; Liver cancer; Medical schools; Medicine and Health Sciences; Metastasis; Micelles; Minimum inhibitory concentration; Nanoparticles; Particle Size; Penetration; Pharmaceutical sciences; Polyethylene glycol; Quercetin; Quercetin - administration & dosage; Radio frequency; Radiofrequency ablation; Rats; Rats, Inbred F344; Studies; Survival; Tumors; Ultrasonic imaging; Xenograft Model Antitumor Assays
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0102727

To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs. Fischer 344 rats were used (n = 196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of i.v. fluorescent beads (20, 100, and 500 nm), with fluorescent intensity measured at 4-24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm) or liposomal (100 nm) preparations of doxorubicin (Dox; targeting HIF-1α) or quercetin (Qu; targeting HSP70). Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg i.v., 15 min post-RFA), and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg i.v.). Tumor coagulation and HIF-1α or HSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with i.v. Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA) compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4-72 hr. Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm) and liver (100 nm) (p