Keila Isaac-Olivé

Multifunctional targeted therapy system based on 99mTc/177Lu-labeled gold nanoparticles-Tat(49–57)-Lys3-bombesin internalized in nuclei of prostate cancer cells

Radiolabeled gold nanoparticles may function simultaneously as radiotherapy and thermal ablation systems. The gastrin-releasing peptide receptor (GRP-r) is overexpressed in prostate cancer, and Lys(3) -bombesin is a peptide that binds with high affinity to the GRP-r. HIV Tat(49-57) is a cell-penetrating peptide that reaches the DNA. In cancer cells, (177) Lu shows efficient crossfire effect, whereas (99m) Tc that is internalized in the cancer cell nuclei acts as an effective system of targeted radiotherapy because of the biological Auger effect. The aim of this research was to evaluate the in vitro potential of (99m) Tc-labeled and (177) Lu-labeled gold nanoparticles conjugated to Tat(49-57)-Lys(3) -bombesin peptides ((99m) Tc/(177) Lu-AuNP-Tat-BN) as a plasmonic photothermal therapy and targeted radiotherapy system in PC3 prostate cancer cells. Peptides were conjugated to AuNPs (5 nm) by spontaneous reaction with the thiol group of cysteine (Cys). The effect on PC3 cell viability after laser heating of the AuNP-Tat-BN incubated with the cancer cells was conducted using an Nd:YAG laser pulsed for 5 ns at 532 nm (0.65 W/cm(2) ). For the (99m) Tc/(177) Lu-AuNP-Tat-BN to be obtained, the (177) Lu-DOTA-Gly-Gly-Cys and (99m) Tc-HYNIC-octreotide radiopeptides were first prepared and added simultaneously to a solution of AuNP-Tat-BN. (99m) Tc/(177) Lu-AuNP-Tat-BN (20 Bq/cell) was incubated with PC3 cells, and the effect on the cell proliferation was evaluated after 3 days. Fluorescence images of (99m) Tc/(177) Lu-AuNP-Tat-BN internalized in nuclei of PC3 were also obtained. After laser irradiation, the presence of AuNP-Tat-BN caused a significant increase in the temperature of the medium (46.4 vs 39.5 °C of that without AuNP) resulting in a significant decrease in PC3 cell viability down to 1.3%. After treatment with (99m) Tc/(177) Lu-AuNP-Tat-BN, the PC3 cell proliferation was inhibited. The nanosystem exhibited properties suitable for plasmonic photothermal therapy and targeted radiotherapy in the treatment of prostate cancer.

Tillandsia usneoides L, a biomonitor in the determination of Ce, La and Sm by neutron activation analysis in an industrial corridor in Central Mexico.

The atmosphere of the Tula Industrial Corridor in Central Mexico is contaminated due to several industries including oil refining while station monitoring in this area are limited. Lanthanides are considered fingerprint of oil refinery activities, and La, Ce and Sm have been previously detected in this area using filters. The suitability of T. usneoides as a biomonitor assessing the La, Ce and Sm concentrations in Particulate Matter is evaluated by NAA. Results of both biomonitor and filters are highly correlated.

Synthesis and evaluation of Lys¹(α,γ-Folate)Lys³(¹⁷⁷Lu-DOTA)-Bombesin(1-14) as a potential theranostic radiopharmaceutical for breast cancer.

The aim of this work was to synthesize Lys(1)(α,γ-Folate)-Lys(3)((177)Lu-DOTA)-Bombesin (1-14) ((177)Lu-Folate-BN), as well as to assess its potential for molecular imaging and targeted radiotherapy of breast tumors expressing folate receptors (FR) and gastrin-releasing peptide receptors (GRPR). Radiation absorbed doses of (177)Lu-Folate-BN (74 MBq, i.v.) estimated in athymic mice with T47D-induced breast tumors (positive to FR and GRPR), showed tumor doses of 23.9±2.1 Gy. T47D-tumors were clearly visible (Micro-SPECT/CT images). (177)Lu-Folate-BN demonstrated properties suitable as a theranostic radiopharmaceutical.

Fluorescent, Plasmonic, and Radiotherapeutic Properties of the 177Lu–Dendrimer-AuNP–Folate–Bombesin Nanoprobe Located Inside Cancer Cells:

The integration of fluorescence and plasmonic properties into one molecule is of importance in developing multifunctional imaging and therapy nanoprobes. The aim of this research was to evaluate the fluorescent properties and the plasmonic–photothermal, therapeutic, and radiotherapeutic potential of 177Lu–dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity (177Lu–DenAuNP–folate–bombesin) when it is internalized in T47D breast cancer cells. The intense near-Infrared (NIR) fluorescence emitted at 825 nm from the conjugate inside cells corroborated the usefulness of DenAuNP–folate–bombesin for optical imaging. After laser irradiation, the presence of the nanosystem in cells caused a significant increase in the temperature of the medium (46.8°C, compared to 39.1°C without DenAuNP–folate–bombesin, P < 0.05), resulting in a significant decrease in cell viability (down to 16.51% ± 1.52%) due to the 177Lu–DenAuNP–folate–bombesin plasmonic properties. After treatment with 177Lu–DenAuNP–folate–bombesin, the T47D cell viability decreased 90% because of the radiation-absorbed dose (63.16 ± 4.20 Gy) delivered inside the cells. The 177Lu–DenAuNP–folate–bombesin nanoprobe internalized in cancer cells exhibited properties suitable for optical imaging, plasmonic–photothermal therapy, and targeted radiotherapy.

Determination of the Residual Anthracene Concentration in Cultures of Haloalkalitolerant Actinomycetes by Excitation Fluorescence, Emission Fluorescence, and Synchronous Fluorescence: Comparative Study

Polycyclic aromatic hydrocarbons (PAHs) are compounds that can be quantified by fluorescence due to their high quantum yield. Haloalkalitolerant bacteria tolerate wide concentration ranges of NaCl and pH. They are potentially useful in the PAHs bioremediation of saline environments. However, it is known that salinity of the sample affects fluorescence signal regardless of the method. The objective of this work was to carry out a comparative study based on the sensitivity, linearity, and detection limits of the excitation, emission, and synchronous fluorescence methods, during the quantification of the residual anthracene concentration from the following haloalkalitolerant actinomycetes cultures Kocuria rosea, Kocuria palustris, Microbacterium testaceum, and 4 strains of Nocardia farcinica, in order to establish the proper fluorescence method to study the PAHs biodegrading capacity of haloalkalitolerant actinobacteria. The study demonstrated statistical differences among the strains and among the fluorescence methods regarding the anthracene residual concentration. The results showed that excitation and emission fluorescence methods performed very similarly but sensitivity in excitation fluorescence is slightly higher. Synchronous fluorescence using Δλ = 150 nm is not the most convenient method. Therefore we propose the excitation fluorescence as the fluorescence method to be used in the study of the PAHs biodegrading capacity of haloalkalitolerant actinomycetes.

In vitro and in vivo synergistic effect of radiotherapy and plasmonic photothermal therapy on the viability of cancer cells using 177Lu–Au-NLS-RGD-Aptamer nanoparticles under laser irradiation

This research aimed to evaluate the photothermal and radiotherapeutic effect of the 177Lu–Au-RGD-NLS-Aptamer anti-angiogenic nanosystem on the viability of U87MG cancer cells by using in vitro and in vivo models, as well as to assess the synergic effect of both therapies. In vitro results demonstrated a decrease in cell viability to 2.14 ± 0.27% after the treatment with photothermal therapy plus radiotherapy. These results correlated with the observed in vivo therapeutic response in mice with U87MG-induced tumors, in which 177Lu–Au-RGD-NLS-Aptamer under laser irradiation inhibited tumor progression. The combination of radiotherapy and thermotherapy in one nanoradiopharmaceutical could be potentially useful for cancer treatment.

BÚSQUEDA DE CAPACIDAD PRODUCTORA DE BIOSURFACTANTES EN ACTINOBACTERIAS HALOALCALÓFILAS Y HALOALCALOTOLERANTES

Una opcion para biorremediar ambientes salinos contaminados con compuestos organicos hidrofobicos, es el uso de microorganismos haloalcalofilos o haloalcalotolerantes capaces de producir biosurfactantes estables y consumir al compuesto hidrofobo. El biosurfactante solubiliza al contaminante haciendolo biodisponible para el microrganismo. De estudios previos se conocia la capacidad de siete actinobacterias haloalcalotolerantes para transformar el antraceno. En este trabajo, a estas siete mas 11 mas aisladas de ambientes salinos, se les determino la capacidad para producir biosurfactantes con propiedades emulsificantes. A las que la mostraron, fueron seleccionadas para saber si utilizaban al antraceno como unica fuente de carbono y energia. La capacidad para producir biosurfactante fue determinada por los metodos de actividad hemolitica, gota colapsada y difusion del diametro de la gota. La propiedad emulsificante y la estabilidad de la emulsion se caracterizaron con el indice de emulsificacion y el indice de emulsificacion relativo, respectivamente. De 18 actinobacterias evaluadas, cinco cepas mostraron capacidad para producir biosurfactantes con propiedades emulsificantes, alta estabilidad en la emulsion y utilizacion de antraceno como unica fuente de carbono y energia. De estas cinco, dos son haloalcalofilas pertenecientes a la especie Nocardiopsis salina y tres son haloalcalotolerantes pertenecientes a las especies: Kocuria palustris, Microbacterium testaceum y Kocuria rosea. En un estudio previo se determino la capacidad transformadora de antraceno en las tres cepas haloalcalotolerantes, por lo tanto los resultados de este estudio sugieren proponerlas como candidatas para procesos de biorremediacion de ambientes salinos contaminados con compuestos hidrofobos. Asimismo se sugiere determinar la misma capacidad para las dos cepas haloalcalofilas.

Detection of Pharmaceuticals in the Environment

In this chapter, for articles addressing drugs as pollutants of natural and wastewater, we discuss the temporal distribution of studies, as well as the main countries of origin for such studies. Focus is given to those articles with more than 200 citations. The main sampling techniques, sample extraction, and detection methods accepted by the USEPA and USGS (based on LC-MS/MS and LC-MS) are reviewed, as well as those methods not based on MS, between 2014 and 2017. From this analysis, we propose directions for future research. Finally, a case study is presented that addresses the analysis of the surface waters of the Izucar de Matamoros region and the Atoyac River in Puebla, as well as the Zahuapan River in Tlaxcala, Mexico. By GC/MS, quantitative determination of naproxen, diclofenac, and triclosan, at stations on the Zahuapan (Tlaxcala), Atoyac, and Nexapa (Puebla) rivers, was performed during the period of 2012–2013. We found that 30% of the publications related with drugs as pollutants of natural and wastewater were published between 2014 and 2017. Spain has published the most of such articles (accounting for 25% of all publications). Three of the articles have more than 1,000 citations. HPLC/MS/MS was the most commonly used method, followed by GC/MS. However, less sophisticated detection alternatives were also used. GC/MS was used to demonstrate the presence of naproxen, diclofenac, triclosan, and carbamazepine in the Mexican Central Plateau and the inability of the wastewater treatment plants (WWTPs) to remove completely these contaminants.

Study of the Optical Properties of Functionalized Gold Nanoparticles in Different Tissues and Their Correlation with the Temperature Increase

Mie theory explains the interaction of light with a gold nanoparticle (AuNP) through the absorption , scattering , and extinction cross sections. These parameters have been calculated in the case of AuNPs dispersed in homogeneous media, but not for specific tissues. The aim of this research was to theoretically obtain the optical cross sections (,, and ) of functionalized AuNPs in liver and colon tissues through Mie theory and correlate them with the temperature increase observed experimentally in tissues containing AuNPs under plasmonic photothermal irradiation using a Nd-YAG laser (λ = 532 nm). Calculations showed that represents % of at 532 nm. The value for a functionalized AuNP in water was 365.66 nm2 (94% of the theoretical maximum value at 522.5 nm), 404.24 nm2 in colon (98% of the theoretical maximum value at 525 nm), and 442.39 nm2 in liver (96% of the theoretical maximum value at 525 nm). Therefore, nanoparticles irradiated at 532 nm are very close to their resonance value. These results correlated with the experimental irradiation of functionalized AuNPs in different tissues, where the average temperature increase showed the pattern liver > colon > water. The temperature increase observed ( up to 13°C) is sufficient to produce cellular death.

Preliminary Analysis of the Social and Scientific Impact of the UAEM‐ININ M.Sc. and D.Sc. Graduate Programme in Medical Physics

Sponsored by the International Atomic Energy Agency (IAEA) in 1994, the Instituto Nacional de Investigaciones Nucleares (ININ) started in Mexico a teaching and training programme (Diplomado) in Radiotherapy Medical Physics. Based on this experience, the Universidad Autonoma del Estado de Mexico (UAEM) and the Instituto Nacional de Investigaciones Nucleares (ININ) launched two years later, the first Graduate Programme in Science (M.Sc. and D.Sc.), specialised in Medical Physics in Mexico. A preliminary analysis of the social and scientific impact of the UAEM‐ININ Programme is presented in this work based on the achievements attained, regarding the number of graduated Medical Physicists, their geographic and academic origin, their current professional activities and the number of scientific publications produced as a result of the thesis, as well as their citations.