6th Iberian Meeting of Colloids and Interfaces - RIC16: book of abstracts

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DESARROLLO DE UN DETECTOR FLEXIBLE DE FOTONES GAMMA BASADO EN FIBRAS ÓPTICAS PLÁSTICAS

Se desarrolló un detector de fotones gamma con características técnicas competitivas similar a los detectores que incluyen los materiales más usados para imagen nuclear. Asimismo, se desarrolló un sistema que basado en fibras ópticas centellográficas, el cual puede dar lugar a un sistema de sonda de detección de blancos moleculares de dimensiones pequeñas.Introduction: Nuclear imaging is based on the principle of detection of radionuclides integrated in specific recognition molecules in patients. Detection devices such as positron emission tomography and single photon emission tomography (PET, SPECT for their acronym in English) are made up of scintillating materials, mostly of the inorganic type, such as NaI(Tl) and the transducer known as a photomultiplier tube (PMT). The purpose of this work was to implement the novel options, which are analogous to the main components of the detecting devices for nuclear imaging studies. In addition to improvements in the acquisition of images for targets of small dimensions (<3 mm), reduce operating times, as well as study costs. The main materials proposed to achieve these objectives are, the scintillating plastic optical fibers and the avalanche photodiodeCONACYT, Instituto Nacioal de Investigaciones Nucleares, Universidad Autónoma del Estado de Méxic

Cancer Nanomedicine

This special issue brings together cutting edge research and insightful commentary on the currentl state of the Cancer Nanomedicine field

Block Copolymer Based Magnetic Nanoclusters for Cancer-Theranostics: Synthesis, Characterization and In Vitro Evaluation

“There is plenty of room at the bottom”. In this visionary lecture in 1959 Prof. Richard Feynman spoke of the interesting ramifications of working with matter at the atomic scale. Since then, scientists have worked relentlessly towards realizing his vision. The influence of nanobiotechnology on material science and polymer chemistry has given rise to a new field called ‘theranostics’, combining drug delivery and diagnostics within the same nanostructures, thereby enabling simultaneous diagnosis, targeted drug delivery and continued therapy monitoring. Iron oxide nanoparticles (MNPs) are one such class of MRI contrast agents that can be converted into theranostic nanomedicines for cancer therapy. However, development of a stable theranostic contrast system comprising of MNPs is complex and requires a careful balance between the therapeutic diagnostic components. We explored the potential of biodegradable hydrophilic block ionomers such as anionic poly (glutamic acid-b-ethylene glycol) and cationic poly (l-lysine-b-ethylene glycol) in formulating stable magnetic nanoclusters (MNCs). These MNCs were extensively characterized for their composition, colloidal stability and factors influencing their MRI capability. Extensive in vitro studies revealed that the anionic cisplatin-loaded MNCs showed minimal non-specific uptake, a highly preferred feature for targeted cancer therapy. Luteinizing hormone releasing hormone receptor (LHRHr) targeting significantly enhanced the uptake of these formulations in LHRHr-positive ovarian cancer cells. LHRHr targeting also helped improve the theranostic efficacy in cisplatin resistant ovarian cancer cells. One the other hand, cationic MNCs were used to demonstrate the potential of MNCs to function as stimuli-responsive theranostic systems capable of releasing the payload in the acidic milieu breast and ovarian cancer cells. These cationic MNCs also exhibited significantly enhanced T2-weighted MRI contrasts at much lower concentrations than the anionic counterparts. Finally, we successfully evaluated the feasibility of kinetically controlled flash nanoprecipitation technique using multi-inlet vortex mixer (MIVM) to formulate well-defined MNCs from non-ionic amphiphilic Pluronic tri-block copolymers. In comparison to self-assembly techniques, flash nanoprecipitation resulted in significant reduction in polydispersity. It was observed that the hydrophobic block-length of the copolymer dictates the extent of encapsulation hydrophobic therapeutic agents along with the MNPs. exhibited the potential to function as both T1 and T2 contrast agents. In summary, looking at the bigger picture, the work presented here emphasizes on the importance of product development in establishing a critical balance between the therapeutic and imaging functionalities when designing an efficient targeted theranostic nanosystems

Novel Detection and Treatment Strategies for Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with an estimated 5-year survival rate of less than 9%. The high lethality of PDAC is due to two primary reasons: the discovery of PDAC at later stages, with locally invasive or metastatic disease present at the time of initial diagnosis as well as the lack of efficacious therapeutic interventions that significantly impact survival. In this dissertation, we sought to discover and test novel detection and treatment strategies for PDAC. Firstly, serum EVs were investigated as potential non-invasive liquid biopsy biomarkers, to serve as a means of early cancer detection. Secondly, a recently discovered form of cell death, ferroptosis, was investigated as a means of potentiating radiation therapy. The investigation into the potential of extracellular vesicles (EVs) as circulating biomarkers began with a label-free analysis of EVs via surface-enhanced Raman Spectroscopy (SERS) and principal component discriminant function analysis (PC-DFA), to identify tumor-specific spectral signatures. This method differentiated EVs originating from PDAC or normal pancreatic epithelial cell lines with 90% overall accuracy. The proof-of-concept application of this method to EVs purified from patient serum exhibited up to 87% and 90% predictive accuracy for healthy control and early PDAC individual samples, respectively. The specific EV surface proteins that may contribute to the observed SERS differences were investigated via surface shaving LC-MS/MS. This analysis provided protein targets that were selected and validated with a combination of bioinformatics, western blot, and immunogold labeling techniques. The first target protein selected for assessment via ELISA, EPHA2, showed elevated expression in complete cancer patient serum as compared to benign controls. Further, EV specific EPHA2 expression was capable of predicting cancer status in 25% (5/20) of the patient samples with 100% specificity. These data suggest a potential role of EV surface profiling for the early detection of PDAC. However, further work is required to increase the overall accuracy. Additionally, we sought to investigate the involvement of ferroptosis, in radiation-induced cell death. Ferroptosis is a non-apoptotic form of cell death that requires labile ferrous iron (Fe2+) and is caused by the reactive oxygen species (ROS) mediated build-up of lipid hydroperoxides. Further, we tested if the pharmaceutical induction of ferroptosis via the small molecule Erastin can potentiate the lethal effects of radiation in vitro and in vivo. We observed that radiation produces an increase in ROS and free Fe2+ leading to lipid hydroperoxidation, which was enhanced with the addition of Erastin culminating in the likely induction of ferroptosis. The combination of radiation and Erastin synergistically increased cell death in monocultures and patient-derived organoids as well as significantly reduced tumor size in xenograft mouse models. These findings suggest the potential of ferroptosis induction to improve radiation therapy, though specific mechanistic components require further evaluation. Therefore, further studies must be conducted to elucidate the specific role of ferroptosis in radiation-induced cell death. The combination of early detection and novel therapeutic intervention strategies offers a means of improving the survival of those with this dreaded disease

Biodegradable Magneto-Luminescent Mesoporous Nanoparticles As New Nanobiomedical Tools In Cancer Treatment

Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide and 2nd in mortality rate, accounting to 1.93 million cases and 916 000 deaths just in 2020. The development of CRC targeted therapies has been a hot topic in recent medical forums and among researchers, with the demand for non-invasive approaches, like oral ones, capable of preserving their therapeutic properties from administration to local action drastically increasing in the last decade. Its body location makes CRC a usually silent disease, whose commonly later detection and action usually lead to severe aggravations and even death. Targetability, drugs' resistance and toxicity of the said therapies are thus three of the key points for the development of effective therapies. On the other hand, the presence of cancerassociated bacterial infections and inflammations has been positively correlated with low treatment success rates and associated complications, with bacterial infections being particularly damaging in gastric and colorectal cancer. Some of the metabolites/toxins of these opportunistic bacteria have been linked to tumorigenesis and CRC drug-resistance. A conjoint therapy capable of addressing both CRC and associated bacteria, where drug preservation, null secondary toxicity and targetability are ensured. In light of the above-mentioned, herein we cover the synthesis of a new magnetofluorescent nanotherapy against both CRC and associated bacterial strains, going from the synthesis of sustainable, biocompatible, biodegradable and cheap nanocomposite particles (NANO3) to the testing of its dual drug cargo and delivery capacities, magneto-fluorescent properties and later assessment of its combined antibacterial and anti-tumor activity. The successful synthesis of new anti-CA IX targeting inhibitor as potential directing agent is also covered as a cheaper alternative to the commonly used and expensive antibodies. From an antimicrobial point of view, NANO3 showed significant activity against CRC-related bacterial strains, with their intrinsic magnetic properties potentiating a hyperthermia-assisted pH responsive release and antimicrobial therapy. The combined release of an antibiotic (i.e., ofloxacin) and an anti-tumor drug (i.e., doxorubicin) showed no hinderance on the activity of both active drugs. Accordingly, NANO3 anti-tumoral activity, arising solely from the loaded doxorubicin, was conserved and competitive to that of the free model drug. Targetability was conferred by successfully functionalizing of NANO3 with anti-EGFR and and/or anti-CA IX, the later favoring higher NANO3 uptake in HCT-116 cell line. A proof-of-concept oral delivery was also simulated, where a dual Eudragit® enteric coating successfully protected NANO3 formulations from stomachal and small intestine conditions, selectively dispensing it in colon environment and potentiating their use in a future anti-CRC oral therapy. In this thesis an optimization of a luminescent antimicrobial activity assay specific for nanoparticles was also carried out along with the evaluation of other cyanine-based antimicrobial scaffolds for a potential biomedical and food-based application.O cancro colorrectal (CRC) é o 3º tipo de cancro mais comum a nível mundial e o 2º na taxa de mortalidade, contabilizando 1,93 milhões de casos e 916 000 mortes apenas em 2020. O desenvolvimento de terapias orientadas para CRC tem sido um tema recorrente no meio médico e entre investigadores, tendo a procura de abordagens não invasivas, tais como as orais, capazes de preservar as suas propriedades terapêuticas desde a administração até à acção local, aumentado drasticamente na última década. A sua localização corporal faz do CRC uma doença geralmente silenciosa, cuja detecção e acção tardias conduzem a agravamentos do quadro clinico ou mesmo à morte. A capacidade de carga, a resistência dos medicamentos e a toxicidade das referidas terapias são assim três dos pontos-chave para o desenvolvimento de terapias eficazes. Por outro lado, a presença de infecções e inflamações bacterianas associadas ao cancro têm sido positivamente correlacionadas com baixas taxas de sucesso de tratamento e ao aumento de complicações, com particular impacto prejudicial em situações de cancro gástrico e colorrectal. Alguns dos metabolitos/toxinas destas bactérias oportunistas têm sido ligados à tumorigenese e à resistência aos medicamentos em CRC. Uma terapia conjunta capaz de tratar tanto CRC como as bactérias associadas, onde a preservação do medicamento, a toxicidade secundária nula e a capacidade de carga são asseguradas. Tendo em conta o acima mencionado, na presente tese detalha-se a síntese de uma nova nanoterapia magneto-fluorescente tanto contra CRC como contra estirpes bacterianas associadas. Indo assim, desde a síntese de partículas nanocompósitas sustentáveis, biocompatíveis, biodegradáveis e baratas (NANO3) até à dupla carga e entrega de medicamentos; bem como da avaliação das suas propriedades magneto-fluorescentes até à sua actividade antibacteriana e antitumoral combinada. A síntese bem-sucedida do novo inibidor de CA IX como potencial agente dirigente é também coberta como uma alternativa mais barata aos anticorpos normalmente utilizados. De um ponto de vista antimicrobiano, NANO3 mostrou uma actividade significativa contra estirpes bacterianas relacionadas com CRC, com as suas propriedades magnéticas intrínsecas potenciando uma libertação pHresponsiva, assistida por hipertérmia, e por fim a uma terapia antimicrobiana. A libertação combinada de um antibiótico (i.e.,, ofloxacina) e de um medicamento anti-tumoral (i.e., doxorubicina) não levou a qualquer redução da actividade de ambos os medicamentos. Assim, a actividade anti-tumoral de NANO3, proveniente unicamente da doxorubicina carregada, foi conservada e competitiva em relação à do medicamento livre. A capacidade de atuar especificamente sobre células de CRC foi conferida pela funcionalização das NANO3 com anti-EGFR e / ou anti-CA IX, o último dos quais favorecendo uma maior internalização de NANO3 na linha celular HCT-116. Foi também simulada uma prova de conceito de uma toma oral, onde um revestimento entérico duplo de Eudragit® protegeu com sucesso as formulações de NANO3 das condições estomacais e do intestino delgado, dispensando-o selectivamente em ambiente de cólon e potenciando a sua utilização numa futura terapia oral anti-CRC. Na presente tese foi também realizada uma optimização de um ensaio de actividade antimicrobiana luminescente específico para nanopartículas, juntamente com a avaliação de outros substratos antimicrobianos à base de cianina para uma potencial aplicação biomédica e alimentar

Application of Nanomaterials in Biomedical Imaging and Cancer Therapy

To mark the recent advances in nanomaterials and nanotechnology in biomedical imaging and cancer therapy, this book, entitled Application of Nanomaterials in Biomedical Imaging and Cancer Therapy includes a collection of important nanomaterial studies on medical imaging and therapy. The book covers recent works on hyperthermia, external beam radiotherapy, MRI-guided radiotherapy, immunotherapy, photothermal therapy, and photodynamic therapy, as well as medical imaging, including high-contrast and deep-tissue imaging, quantum sensing, super-resolution microscopy, and three-dimensional correlative light and electron microscopy. The significant research results and findings explored in this work are expected to help students, researchers and teachers working in the field of nanomaterials and nanotechnology in biomedical physics, to keep pace with the rapid development and the applications of nanomaterials in precise imaging and targeted therapy

Advances in Nanogels

In the last two decades, nanogels have emerged as very promising and versatile biomaterials suitable for a wide range of applications. Their features, such as large surface areas, the ability to hold molecules, flexibility in their size and their water-based formulations, have earned them great recognition as drug delivery systems for various in vivo applications, confirming their potential. On the other hand, because of their tuneable and versatile characteristics, nanogels have been investigated in recent years for applications in various fields other than biomedicine. In view of this variety of possible applications of nanogels, in this Special Issue, we extend our knowledge on the topic of their possible uses described in literature, taking stock of the state-of-the-art for all possible nanogel applications and their synthesis methods