Therapeutic nanostructures and nanotoxicity.

Nanotechnology, with its continuous advancement, leads to the development of nanoscale-level therapeutics to mitigate many complex diseases. This results in the emergence of numerous novel nanomaterials and its composite products into the market such as liposome, polymeric nanoparticles, dendrimers, and nanostructured lipid carrier. However, their application is always determined by a high benefit to risk ratio. Very few research have been done on the toxicity assessment of nanoparticles in the biological system; therefore, the limited knowledge regarding the toxicity profile of nanotherapeutics is available leading to the ignorance of its side effects. Nanoparticles can distribute in the whole body through translocating in the bloodstream by crossing membrane barriers efficiently and shows effect in organs and tissues at cellular and molecular levels. The interaction of nanoparticle with cell may consequences into nanotoxicity. The narrow size distribution, large surface area to mass ratio and surface properties of nanoparticle are significantly associated with nanotoxicity. Nanoparticles can enter into the tissue and cell by invading the membranes and cause cellular injury as well as toxicity. Therefore, the exploration of mechanisms of nanotoxicity has prime importance now a day. The toxicity assessment should be an integral part of the development of nanotherapeutics using various toxicity evaluation models. This review has focused on the exploration of different nanostructures for therapeutic delivery system along with its physicochemical characteristics responsible for adverse effects on human biology, various toxicity evaluation models, and environmental and regulatory hurdles.

Predictors of Prostate-specific Membrane Antigen (PSMA/FOLH1) Expression in a Genomic Database.

OBJECTIVE: To assess predictors of prostate-specific membrane antigen (PSMA) expression in a genomic database; positron emission tomography with PSMA-targeted radiopharmaceuticals is increasingly being utilized. METHODS: The de-identified Decipher Biosciences database, which includes expression for more than 46,000 coding and noncoding genes per patient, was queried for expression of FOLH1 (PSMA). Prostate cancer patients who underwent radical prostatectomy and received the Decipher Test were included in the analysis. PSMA expression was compared to the Gleason Grade Group, Decipher risk category (a validated 22 biomarker genomic score), basal versus luminal molecular subtype, and androgen receptor activity. Multivariable regression analyses were performed. RESULTS: The Decipher de-identified Decipher Biosciences database contained 16,807 men who underwent prostatectomy with the average age being 65-year old and most being Gleason Grade Group 2 (35%) or 3 (27%). Higher Grade Group was associated with higher PSMA expression except in Grade Group 5 [Grade group: 1 (0.66), 2 (0.84), 3 (0.99), 4 (1.07), 5 (0.99), P <.001]. Luminal subtype was found to have much higher PSMA expression when compared to basal (1.01 vs 0.68, P <.001). The androgen receptor activity signature demonstrated a dramatic difference between basal (0.19) and luminal (0.62) subtypes (P <.001). In the multivariable model, luminal patients, high androgen receptor activity scores, and high Grade Groups were significantly associated with higher FOLH1 percentile rank (P <.001). CONCLUSION: High PSMA expression (FOLH1) was associated with high androgen receptor activity and luminal subtype. Genomic tests could aid in predicting, interpreting, and/or directing PSMA theranostics.

Glucose Oxidase-Instructed Traceable Self-Oxygenation/Hyperthermia Dually Enhanced Cancer Starvation Therapy.

Cancer theranostics based on glucose oxidase (GOx)-induced starvation therapy has got more and more attention in cancer management. Herein, GOx armed manganese dioxide nanosheets (denoted as MNS-GOx) were developed as cancer nanotheranostic agent for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided self-oxygenation/hyperthermia dually enhanced starvation cancer therapy. The manganese dioxide nanomaterials with different morphologies (such as nanoflowers, nanosheets and nanowires) were synthesized by a biomimetic approach using melanin as a biotemplate. Afterwards, the manganese dioxide nanosheets (MNS) with two sides and large surface area were selected as the vehicle to carry and deliver GOx. The as-prepared MNS-GOx can perform the circular reaction of glucose oxidation and H2O2 decomposition for enhanced starvation therapy. Moreover, the catalytic activity of GOx could be further improved by the hyperthermia of MNS-GOx upon near-infrared laser irradiation. Most intriguingly, MNS-GOx could achieve "turn-on" MR imaging and "turn-off" PA imaging simultaneously. The theranostic capability of MNS-GOx was evaluated on A375 tumor-bearing mice with all tumor elimination. Our findings integrated molecular imaging and starvation-based synergistic cancer therapy, which provided a new platform for cancer nanotheranostics.

Integration of Fricke gel dosimetry with Ag nanoparticles for experimental dose enhancement determination in theranostics.

The use and implementation of nanoparticles in medicine has grown exponentially in the last twenty years. Their main applications include drug delivery, theranostics, tissue engineering and magneto function. Dosimetry techniques can take advantage of inorganic nanoparticles properties and their combination with gel dosimetry techniques could be used as a first step for their later inclusion in radio-diagnostics or radiotherapy treatments. The present study presents preliminary results of properly synthesized and purified silver nanoparticles integration with Fricke gel dosimeters. Used nanoparticles presented mean sizes ranging from 2 to 20 nm, with a lognormal distribution. Xylenol orange concentration in Fricke gel dosimeter was adjust in order to allow sample's optical readout, accounting nanoparticles plasmon. Dose enhancement was assessed irradiating dosimeters setting X-ray beams energies below and above silver K-edge. Monte Carlo simulations were used to estimate the dose enhancement in the experiments and compare with the trend obtained in the experimental results.