Abstract:Cryosurgery is a minimally invasive cancer treatment using cryogenic temperatures. Intraoperative monitoring of iceball growth is an advantage of the treatment.
“…The male athymic nude mice (NU/J, The Jackson Laboratory, Bar Harbor, Maine, USA) weighing 20 to 25 g were housed according to these procedures. One mouse was used for proof-of-principle imaging experiments and received subcutaneous, hindlimb injections of 1 million LNCaP cells, prepared as previously described 34,39 . Experiments were conducted after about 6 weeks and the tumors had reached an average diameter of about 7 mm.…”
Aggregation is a known consequence of nanoparticle use in biology and medicine; however, nanoparticle characterization is typically performed under the pretext of well-dispersed, aqueous conditions. Here, we systematically characterize the effects of aggregation on the alternating magnetic field induced heating and magnetic resonance (MR) imaging performance of iron oxide nanoparticles (IONPs) in non-ideal biological systems. Specifically, the behavior of IONP aggregates composed of ~10 nm primary particles, but with aggregate hydrodynamic sizes ranging from 50 nm to 700 nm, was characterized in phosphate buffered saline and fetal bovine serum suspensions, as well as in gels and cells. We demonstrate up to a 50% reduction in heating, linked to the extent of aggregation. To quantify aggregate morphology, we used a combination of hydrodynamic radii distribution, intrinsic viscosity, and electron microscopy measurements to describe the aggregates as quasifractal entities with fractal dimensions in the 1.8–2.0 range. Importantly, we are able to correlate the observed decrease in magnetic field induced heating with a corresponding decrease in longitudinal relaxation rate (R1) in MR imaging, irrespective of the extent of aggregation. Finally, we show in vivo proof-of-principle use of this powerful new imaging method, providing a critical tool for predicting heating in clinical cancer hyperthermia.
“…The male athymic nude mice (NU/J, The Jackson Laboratory, Bar Harbor, Maine, USA) weighing 20 to 25 g were housed according to these procedures. One mouse was used for proof-of-principle imaging experiments and received subcutaneous, hindlimb injections of 1 million LNCaP cells, prepared as previously described 34,39 . Experiments were conducted after about 6 weeks and the tumors had reached an average diameter of about 7 mm.…”
Aggregation is a known consequence of nanoparticle use in biology and medicine; however, nanoparticle characterization is typically performed under the pretext of well-dispersed, aqueous conditions. Here, we systematically characterize the effects of aggregation on the alternating magnetic field induced heating and magnetic resonance (MR) imaging performance of iron oxide nanoparticles (IONPs) in non-ideal biological systems. Specifically, the behavior of IONP aggregates composed of ~10 nm primary particles, but with aggregate hydrodynamic sizes ranging from 50 nm to 700 nm, was characterized in phosphate buffered saline and fetal bovine serum suspensions, as well as in gels and cells. We demonstrate up to a 50% reduction in heating, linked to the extent of aggregation. To quantify aggregate morphology, we used a combination of hydrodynamic radii distribution, intrinsic viscosity, and electron microscopy measurements to describe the aggregates as quasifractal entities with fractal dimensions in the 1.8–2.0 range. Importantly, we are able to correlate the observed decrease in magnetic field induced heating with a corresponding decrease in longitudinal relaxation rate (R1) in MR imaging, irrespective of the extent of aggregation. Finally, we show in vivo proof-of-principle use of this powerful new imaging method, providing a critical tool for predicting heating in clinical cancer hyperthermia.
“…As in Antonii's day, gold nanoparticles are being used for a variety of medical purposes, which offer some of the most promising applications of gold nanomaterials. To date gold nanoparticles have been used in the treatment of cancerous tumors by photo-thermal ablation (El-Sayed et al 2006), imaging (Keren et al 2008), drug delivery for hypothermia (Pedro et al 2010), and hyperthermia (Goel et al 2007).…”
Gold nanoparticles were synthesized by a hot-wire generator at atmospheric pressure using a gold-platinum composite wire. At low gas flow velocities the nanoparticles were found to be agglomerates of partially sintered primary particles. By reducing the tube size via the insertion of a nozzle with a throat diameter of 3 mm, the hot-wire generator was found to produce small (<10 nm diameter) crystalline gold particles. Elemental and x-ray photoelectron spectroscopy analysis of the particles showed that they were composed of gold with no platinum impurity. Charging analysis of the "as-produced" nanoparticles showed that fewer than 10% of the particles were charged, but the charge fraction increased as the applied power increased, as did the ratio of negatively-topositively-charged particles.
“…But like many other stand–alone cytotoxic drugs used in cancer treatment, the systemic delivery of required amounts of TNF-α is a major obstacle to achieve rapid clinical translation of this finding. In a recent study, targeted delivery of TNF-α was performed using gold nanoparticles coated with the drug that achieved a similar augmentation in tissue injury and greatly reduced systemic side effects [98]. More studies are needed in translational models to optimize dosage and advance this cryoadjuvant approach into clinic.…”
Section: Adjuvants With Cryosurgerymentioning
confidence: 99%
“…If performing a localized delivery, the number of injections or implants and their precise locations will likely require incorporation within a the 3D computerized planning of the overall treatment. For thermophysical adjuvants, delivery is a big constraint as the adjuvant dosages that have been shown to be effective in vitro are relatively higher (mg per g of tissue) than other groups (μg per g of tissue) [42, 44, 98]. Both local and systemic delivery approaches are possible options.…”
Molecular adjuvants can be used to enhance the natural destructive mechanisms of freezing within tissue. This review discusses their use in the growing field of combinatorial or adjuvant enhanced cryosurgery for a variety of disease conditions. Two important motivations for adjuvant use are: (1) increased control of the local disease in the area of freezing (i.e., reduced local recurrence of disease) and (2) reduced complications due to over-freezing into adjacent tissues (i.e., reduced normal functional tissue destruction near the treatment site). This review starts with a brief overview of cryosurgical technology including probes and cryogens and major mechanisms of cellular, vascular injury and possible immunological effects due to freeze-thaw treatment in vivo. The review then focuses on adjuvants to each of these mechanisms that make the tissue more sensitive to freeze-thaw injury. Four broad classes of adjuvants are discussed including: thermophysical agents (eutectic forming salts and amino acids), chemotherapuetics, vascular agents and immunomodulators. The key issues of selection, timing, dose and delivery of these adjuvants are then elaborated. Finally, work with a particularly promising vascular adjuvant, TNF-alpha, that shows the ability to destroy all cancer within a cryosurgical iceball is highlighted.
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