Review of Advances in Coating and Functionalization of Gold Nanoparticles: From Theory to Biomedical Application.

Nanoparticles, especially gold nanoparticles (Au NPs) have gained increasing interest in biomedical applications. Used for disease prevention, diagnosis and therapies, its significant advantages in therapeutic efficacy and safety have been the main target of interest. Its application in immune system prevention, stability in physiological environments and cell membranes, low toxicity and optimal bioperformances are critical to the success of engineered nanomaterials. Its unique optical properties are great attractors. Recently, several physical and chemical methods for coating these NPs have been widely used. Biomolecules such as DNA, RNA, peptides, antibodies, proteins, carbohydrates and biopolymers, among others, have been widely used in coatings of Au NPs for various biomedical applications, thus increasing their biocompatibility while maintaining their biological functions. This review mainly presents a general and representative view of the different types of coatings and Au NP functionalization using various biomolecules, strategies and functionalization mechanisms.

Radioactive Seed Localization for Nonpalpable Breast Lesions: Systematic Review and Meta-Analysis.

BACKGROUND: This study is a systematic review with meta-analysis comparing radioactive seed localization (RSL) versus radio-guided occult lesion localization (ROLL) and wire-guided localization (WGL) for patients with impalpable breast cancer undergoing breast-conserving surgery and evaluating efficacy, safety, and logistical outcomes. The protocol is registered in PROSPERO with the number CRD42022299726. METHODS: A search was conducted in the Embase, Lilacs, Pubmed, Scielo, Web of Science, and clinicaltrials.gov databases, in addition to a manual search in the reference list of relevant articles, for randomized clinical trials and cohort studies. Studies selected were submitted to their own data extraction forms and risk of bias analysis according to the ROB 2 and ROBINS 1 tools. A meta-analysis was performed, considering the random effect model, calculating the relative risk or the mean difference for dichotomous or continuous data, respectively. The quality of the evidence generated was analyzed by outcome according to the GRADE tool. Overall, 46 articles met the inclusion criteria and were included in this systematic review; of these, 4 studies compared RSL and ROLL with a population of 1550 women, and 43 compared RSL and WGL with a population of 19,820 women. RESULTS: The results showed that RSL is a superior method to WGL in terms of surgical efficiency in the impalpable breast lesions' intraoperative localization, and it is at least equivalent to ROLL. Regarding security, RSL obtained results equivalent to the already established technique, the WGL. In addition to presenting promising results, RSL has been proven to be superior to WGL and ROLL technologies.

Radioactive gold nanoparticles coated with BSA: A promising approach for prostate cancer treatment.

Background: Nanotechnology has revolutionized medicine, especially in oncological treatments. Gold nanoparticles (AuNPs) stand out as an innovative alternative due to their biocompatibility, potential for surface modification, and effectiveness in radiotherapeutic techniques. Given that prostate cancer ranks as one of the leading malignancies among men, there's a pressing need to investigate new therapeutic approaches. Methods: AuNPs coated with bovine serum albumin (BSA) were synthesized and their cytotoxicity was assessed against prostate tumor cell lines (LNCaP and PC-3), healthy prostate cells (RWPE-1), and endothelial control cells (HUVEC) using the MTS/PMS assay. For in vivo studies, BALB/C Nude mice were employed to gauge the therapeutic efficacy, biodistribution, and hematological implications post-treatment with BSA-coated AuNPs. Results: The BSA-coated AuNPs exhibited cytotoxic potential against PC-3 and LNCaP lines, while interactions with RWPE-1 and HUVEC remain subjects for further scrutiny. Within animal models, a diverse therapeutic response was observed, with certain instances indicating complete tumor regression. Biodistribution data emphasized the nanoparticles' affinity towards particular organs, and the majority of hematological indicators aligned with normative standards. Conclusions: BSA-coated AuNPs manifest substantial promise as therapeutic tools in treating prostate cancer. The present research not only accentuates the nanoparticles' efficacy but also stresses the imperative of optimization to ascertain both selectivity and safety. Such findings illuminate a promising trajectory for avant-garde therapeutic modalities, holding substantial implications for public health advancements.

Radioactive Seed Localization for Conservative Surgery of Nonpalpable Breast Cancer: Recommendations for Technology Implantation Program.

Background: The radioactive seed localization (RSL) is used in impalpable breast cancer conservative surgery to assist the surgeon in accurately locating and excising the lesion site. This study aims to present recommendations about the RSL program implementation in health institutions that perform breast cancer conservative surgery with intraoperative localization. Methods: An extensive literature review was performed. It comprehends: the committee responsible for implementation of the program actions; description of the necessary multidisciplinary team; the radiological safety committee role; the facility licensing; professionals training; material and instrumentation associated with the technique; and seed tracking system. Results: 13 topics are presented. The Program Implementation Committee must be formed by leaders from each department. The committee assumes responsibility for evaluating the necessary processes and presenting the schedule for program implementation. Since the procedure is classified as a nuclear medicine procedure it requires licensing. The Professional Team Formation, Education, and Training is a priority and simulation exercises are necessary. The Materials and Instrumentation Associated with the Technique must be well-know by the team and they should practice using radiation detectors. The seed must be always tracked, from moment they are received to discard. An Inventory for Tracking Seeds is provided. The Radiological Safety Aspects such as the ALARA principle are presented. A full description for the Radiological Procedure for Placing the seeds, the surgical removal and the Specimen Handling in Pathology focusing on how to locate the seed and retrieve them. After removed, the seeds can be placed in storage to wait for full radioactive decay or be returned to the manufacturer. Conclusions: The procedure has the advantage to increase to 2 months the time between insertion of the seed and the surgical removal. Regular multidisciplinary team meetings during program development are important to create a realistic timeline, having briefing meetings after the first 1-5 RSL cases and having annual or biannual follow-up meetings to discuss any issues or incidents. Abstract Graphic ImageCreated by Macrovector, obtained in Freepik at https://br.freepik.com/fotos-vetores-gratis/oncologia.This graphical abstract shows everything that is necessary to implement the RSL technique and are discussed in this paper. Highlights: This study present recommendations for RSL program implementation in hospitalsWas performed by an extensive descriptive and qualitative literature reviewTopics 1: Implementation Committee, Professional Team Training, InstrumentationTopics 2: Radiological Safety, Patient Consent, Radiological ProcessTopics 3: Surgical Procedure, Pathology, Seeds Disposal Completion.

Synthesis, In Vitro Testing, and Biodistribution of Surfactant-Free Radioactive Nanoparticles for Cancer Treatment.

New forms of cancer treatment, which are effective, have simple manufacturing processes, and easily transportable, are of the utmost necessity. In this work, a methodology for the synthesis of radioactive Gold-198 nanoparticles without the use of surfactants was described. The nuclear activated Gold-198 foils were transformed into H198AuCl4 by dissolution using aqua regia, following a set of steps in a specially designed leak-tight setup. Gold-198 nanoparticles were synthesized using a citrate reduction stabilized with PEG. In addition, TEM results for the non-radioactive product presented an average size of 11.0 nm. The DLS and results for the radioactive 198AuNPs presented an average size of 8.7 nm. Moreover, the DLS results for the PEG-198AuNPs presented a 32.6 nm average size. Cell line tests showed no cytotoxic effect in any period and the concentrations were evaluated. Furthermore, in vivo testing showed a high biological uptake in the tumor and a cancer growth arrest.

Photobiomodulation therapy combined with radiotherapy in the treatment of triple-negative breast cancer-bearing mice.

This work investigated the effect of photobiomodulation therapy (PBM) combined with radiotherapy (RT) on triple-negative breast cancer (TNBC)-bearing mice. Female BALB/c mice received 4 T1 cells into a mammary fat pad. Local RT was performed with a total dose of 60 Gy divided into 4 consecutive sessions of 15 Gy. For PBM, a red laser was used in three different protocols: i-) single exposure delivering 150 J.cm-2 (24 h after the last RT session), and ii-) radiant exposure of 150 J.cm-2 or iii-) fractionated radiant exposure of 37.5 J.cm-2 (after each RT session). Tumor volume, complete blood cell count, clinical condition, metastasis, and survival of animals were monitored during 3 weeks post-RT. Our results demonstrated that regardless of the protocol, PBM arrested the tumor growth, improved the clinical condition, and prevented hemolytic anemia. Besides, although PBM groups have exhibited a high neutrophil:lymphocyte ratio (NLR), they decreased the number of lung metastases and enhanced mouse survival. Worthy of note, PBM should be used along with the RT sessions in higher radiant exposures, since PBM at 150 J.cm-2 per session significantly extended the survival rate. Together, these data suggest PBM could be a potential ally to RT to fight TNBC.

Monte Carlo simulation to assess free space and end-weld thickness variation effects on dose rate for a new Ir-192 brachytherapy source.

A new Iridium-192 seed for brachytherapy is under development. Specific dose rate contribution by two different factors were evaluated: the effect from movement of the core in the free space within the seed and the effect of the end-weld thickness variation. Both were investigated through use of the Monte Carlo radiation transport code MCNP6 and an in-house routine programmed with MATLAB. Differences greater than 15% compared to results from the nominal seed were found near the source, indicating a significant dose variation.

Gamma spectrometry of iodine-125 produced in IEA-R1 nuclear reactor, using HPGe detector and fixation into epoxy matrix disc.

Few places in the world produce iodine-125. In Brazil, the first production was achieved by using the IEA-R1 nuclear reactor located at Nuclear and Energy Research Institute - IPEN. To verify the quality of iodine-125 produced, and the amount of contaminants such as iodine-126, cesium-134 and caesium-137 among others, iodine-125 samples were immobilized into epoxy matrix disc, with the same geometry of a barium-133 reference radioactive source, used to calibrate an HPGe detector. The HPGe detector has a thin carbon composite window, which allows measure the iodine-125 photopeaks, between 27.1 and 35.4 keV. The method employed here was successful in producing and measurement of iodine-125.

New model for an epoxy-based brachytherapy source to be used in spinal cancer treatment.

The present work described the cold fabrication of a P-32 radioactive source to be used in CNS cancer using epoxy resin. The epoxy plaque fabricated with Teflon mold presented better agreement. MCNP simulation evaluated the radiation dose. Special attention was given to factors that can impact dose distribution. Average dose was 16.44 ± 2.89% cGy/s. Differences of less than 0.01 cm in thickness within the plaque lead to differences of up to 12% in the dose rate.

New core configuration for the fabrication of 125I radioactive sources for cancer treatment.

In order to provide prostate brachytherapy treatment for more Brazilian men, IPEN is building a laboratory for the manufacture of radioactive sources. The new methodology for the production of iodine-125 seeds with yield 71.7% ± 5.3%. Points of importance were evaluated/discussed: photo-sensibility, reaction vial type, the substitution for iodine-131, pH, and solution volume. The surface was analyzed by FTIR and EDS. At the end, a Monte Carlo-MCNP6 simulation was performed to evaluate the TG-43 parameters.

Highly efficient method for production of radioactive silver seed cores for brachytherapy.

A simple and highly efficient (shorter reaction time and almost no rework) method for production of iodine based radioactive silver seed cores for brachytherapy is described. The method allows almost quantitative deposition of iodine-131 on dozens of silver substrates at once, with even distribution of activity per core and insignificant amounts of liquid and solid radioactive wastes, allowing the fabrication of cheaper radioactive iodine seeds for brachytherapy.

Development of a phantom to validate high-dose-rate brachytherapy treatment planning systems with heterogeneous algorithms.

PURPOSE: This work presents the development of a phantom to verify the treatment planning system (TPS) algorithms used for high-dose-rate (HDR) brachytherapy. It is designed to measure the relative dose in a heterogeneous media. The experimental details used, simulation methods, and comparisons with a commercial TPS are also provided. METHODS: To simulate heterogeneous conditions, four materials were used: Virtual Water™ (VM), BR50/50™, cork, and aluminum. The materials were arranged in 11 heterogeneity configurations. Three dosimeters were used to measure the relative response from a HDR (192)Ir source: TLD-100™, Gafchromic(®) EBT3 film, and an Exradin™ A1SL ionization chamber. To compare the results from the experimental measurements, the various configurations were modeled in the penelope/penEasy Monte Carlo code. Images of each setup geometry were acquired from a CT scanner and imported into BrachyVision™ TPS software, which includes a grid-based Boltzmann solver Acuros™. The results of the measurements performed in the heterogeneous setups were normalized to the dose values measured in the homogeneous Virtual Water™ setup and the respective differences due to the heterogeneities were considered. Additionally, dose values calculated based on the American Association of Physicists in Medicine-Task Group 43 formalism were compared to dose values calculated with the Acuros™ algorithm in the phantom. Calculated doses were compared at the same points, where measurements have been performed. RESULTS: Differences in the relative response as high as 11.5% were found from the homogeneous setup when the heterogeneous materials were inserted into the experimental phantom. The aluminum and cork materials produced larger differences than the plastic materials, with the BR50/50™ material producing results similar to the Virtual Water™ results. Our experimental methods agree with the penelope/penEasy simulations for most setups and dosimeters. The TPS relative differences with the Acuros™ algorithm were similar in both experimental and simulated setups. The discrepancy between the BrachyVision™, Acuros™, and TG-43 dose responses in the phantom described by this work exceeded 12% for certain setups. CONCLUSIONS: The results derived from the phantom measurements show good agreement with the simulations and TPS calculations, using Acuros™ algorithm. Differences in the dose responses were evident in the experimental results when heterogeneous materials were introduced. These measurements prove the usefulness of the heterogeneous phantom for verification of HDR treatment planning systems based on model-based dose calculation algorithms.