Combined Treatment of Tyrosine Kinase Inhibitor-Labeled Gold Nanorod Encapsulated Albumin With Laser Thermal Ablation in a Renal Cell Carcinoma Model

J Pharm Sci. 2016 Jan;105(1):284-92. doi: 10.1016/j.xphs.2015.11.017. Epub 2016 Jan 13.

Abstract

To characterize and evaluate human serum albumin-encapsulated nanoparticles for drug delivery of a tyrosine kinase inhibitor combined with induction of photothermal ablation combination therapy of renal cell carcinoma (RCC), nanoparticles of varying preparations and concentrations were characterized via zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using clear cell RCC cell line RCC 786-0, a human metastatic carcinoma. Target temperatures of >50°C were consistently attained by 0.1 and 0.05 μM concentrations of irradiated human serum albumin nanoparticle-gold nanorods (HSAP-AuNRs). Irradiated trials of HSAP-AuNRs demonstrated significantly decreased cell viabilities compared with nonirradiated "dark" controls (p < 0.01). Increasing loaded masses of sorafenib (SRF) also significantly decreased relative cell viability of RCC (p < 0.05). Photothermal ablation using HSAP-AuNRs is capable of inducing significant hyperthermia while the loading of SRF further enhances cytotoxicity relative to treatment with HSAP-AuNRs alone. HSAP-AuNR-SRFs have the potential to be an effective, novel combination treatment for advanced RCC.

Keywords: gold nanorods; microencapsulation; nanotechnology; photothermal ablation; renal cell carcinoma; sorafenib.

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Coumarins / chemistry
  • Drug Compounding
  • Gold
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Lasers
  • Nanotubes
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Serum Albumin / chemistry
  • Solubility
  • Sorafenib

Substances

  • Antineoplastic Agents
  • Coumarins
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Serum Albumin
  • Niacinamide
  • Gold
  • Sorafenib
  • coumarin
  • Protein-Tyrosine Kinases