Biocompatible gold nanoparticles designed to absorb light at wavelengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance–ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.

Link: https://www.pnas.org/content/early/2019/08/20/1906929116

We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conjugated gold nanorods. Progressive receptor-mediated internalization of conjugated nanorods over time increases the radiation interaction cross-section of cells and contributes to the effects observed in vitro. The low concentrations of gold required, the long interval between injection of nanoparticles and radiation, and the use of megavoltage radiation to generate radiosensitization in vivo foretell the possibility of eventual clinical translation of this approach.

To evaluate the clinical safety profile for the use of gold nanoshells in patients with human prostate cancer. This follows on the nonclinical safety assessment of the AuroShell particles reported previously. Twenty-two patients, with biopsy diagnosed prostate cancer, underwent nanoshell infusion and subsequent radical prostatectomy (RRP). Fifteen of these patients had prostates that were additionally irradiated by a single-fiber laser ablation in each prostate hemisphere prior to RRP. Patients in the study were assessed at 9 time points through 6 months post infusion. Adverse events were recorded as reported by the patients and from clinical observation. Blood and urine samples were collected at each patient visit and subjected to chemical (16 tests), hematological (23 tests), immunological (3 tests, including total PSA), and urinalysis (8 tests) evaluation. Temperature of the anterior rectal wall at the level of the prostate was measured. The study recorded 2 adverse events that were judged attributable to the nanoparticle infusion: (1) an allergic reaction resulting in itching, which resolved with intravenous antihistamines, and (2) in a separate patient, a transient burning sensation in the epigastrium. blood/hematology/urinalysis assays indicated no device-related changes. No change in temperature of the anterior rectal wall was recorded in any of the patients. The clinical safety profile of AuroShell particles is excellent, matching nonclinical findings. A recent consensus statement suggested that the published literature does not support a preference for any ablation technique over another.(1) Now that clinical safety has been confirmed, treatment efficacy of the combined infusion plus laser ablation in prostate will be evaluated in future studies using imaging modalities directing the laser against identified prostate tumors.

We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conjugated gold nanorods. Progressive receptor-mediated internalization of conjugated nanorods over time increases the radiation interaction cross-section of cells and contributes to the effects observed in vitro. The low concentrations of gold required, the long interval between injection of nanoparticles and radiation, and the use of megavoltage radiation to generate radiosensitization in vivo foretell the possibility of eventual clinical translation of this approach.

AIM:
Gold nanoparticles are employed for imaging and treatment of surgically inaccessible tumors owing to their inherent optical absorption and ability to extravasate through intravenous distribution. These nanoparticles are cleared from the blood by the reticuloendothelial system (RES) as expected given their size.

MATERIALS & METHODS:
This study demonstrates the effects of RES blockade through the intravenous administration of λ-carrageenan, resulting in a decrease in the median clearance rate from 18.9 (95% CrI: 15.9-22.6) to 11.2 (95% CrI: 8.8-13.9) μl/min and an increase in nanoparticle circulation half-life t(½)( = 264 ± 73 vs 160 ± 22 min; p < 0.01).

RESULTS:
This 59.3% decrease in clearance is greater than the 15% previously reported for liposomes [ 1 ].

CONCLUSION:
The primary benefit of nontoxic RES blockade is to increase the circulation time, where traditional particle modification is ineffective or impractical.

PURPOSE:
Optically activated nanoparticle-mediated heating for thermal therapy applications is an area of intense research. The ability to characterise the spatio-temporal heating potential of these particles for use in modelling under various exposure conditions can aid in the exploration of new approaches for therapy as well as more quantitative prospective approaches to treatment planning. The purpose of this research was to investigate an inverse solution to the heat equation using magnetic resonance temperature imaging (MRTI) feedback, for providing optical characterisation of two types of nanoparticles (gold-silica nanoshells and gold nanorods).

METHODS:
The optical absorption of homogeneous nanoparticle-agar mixtures was measured during exposure to an 808 nm laser using real-time MRTI. A coupled finite element solution of heat transfer was registered with the data and used to solve the inverse problem. The L2 norm of the difference between the temperature increase in the model and MRTI was minimised using a pattern search algorithm by varying the absorption coefficient of the mixture.

RESULTS:
Absorption fractions were within 10% of literature values for similar nanoparticles. Comparison of temporal and spatial profiles demonstrated good qualitative agreement between the model and the MRTI. The weighted root mean square error was <1.5 σMRTI and the average Dice similarity coefficient for ΔT = 5 °C isotherms was >0.9 over the measured time interval.

CONCLUSION:
This research demonstrates the feasibility of using an indirect method for making minimally invasive estimates of nanoparticle absorption that might be expanded to analyse a variety of geometries and particles of interest.