title: Stability of antibody-conjugated gold nanoparticles in the endolysosomal nanoenvironment: implications for noninvasive radiofrequency-based cancer therapy.
abstract: The use of noninvasive radiofrequency (RF) electric fields as an energy source for thermal activation of nanoparticles within cancer cells could be a valuable addition to the emerging field of nano-mediated cancer therapies. Based on investigations of cell death through hyperthermia, and offering the ability for total-body penetration by RF fields, this technique is thought to complement and possibly outperform existing nano-heat treatments that utilize alternative heat production via optical or magnetic stimuli. However, it remains a challenge to understand fully the complex RF-nanoparticle-intracellular interactions before full system optimization can be engineered. Herein we have shown that liver cancer cells can selectively internalize antibody-conjugated gold nanoparticles (AuNPs) through receptor-mediated endocytosis, with the nanoparticles predominantly accumulating and aggregating within cytoplasmic endolysosomes. After exposure to an external RF field, nonaggregated AuNPs absorbed and dissipated energy as heat, causing thermal damage to the targeted cancer cells. We also observed that RF absorption and heat dissipation is dependent on solubility of AuNPs in the colloid, which is pH dependent. Furthermore, by modulating endolysosomal pH it is possible to prevent intracellular AuNP aggregation and enhance thermal cytotoxicity in hepatocellular cancer cells.
  
  
  BACKGROUND
  Gold nanoparticles absorb energy from RF fields and can exert hyperthermic effects leading to cell death. Combining this known effect with antibody-based targeting of the nanoparticles, selective cancer specific hyperthermia induced cell death therapies can be designed, as demonstrated in this article.
authors.affiliation: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Raoof
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Corr
authors.forename: Warna D
authors.initials: WD
authors.lastname: Kaluarachchi
authors.forename: Katheryn L
authors.initials: KL
authors.lastname: Massey
authors.forename: Katrina
authors.initials: K
authors.lastname: Briggs
authors.forename: Cihui
authors.initials: C
authors.lastname: Zhu
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cheney
authors.forename: Lon J
authors.initials: LJ
authors.lastname: Wilson
authors.forename: Steven A
authors.initials: SA
authors.lastname: Curley
mesh_terms: D000906:Antibodies / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006046:Gold / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced / Q000379:methods*; D018796:Immunoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D000078702:Radiofrequency Therapy; D012995:Solubility
chemical_list: D000906:Antibodies; D018796:Immunoconjugates; D006046:Gold