The NanoPlatforms group conveys expertise on physical-chemistry, medicinal chemistry, pharmaceutical and analytical sciences to support research towards the development of innovative nanoplatforms to address current environmental, food industry and biomedical challenges. The group’s research is focused on the design, synthesis and optimization of inorganic, organic and hybridnanoparticles for multipurpose applications, such as development of plasmonic, electrochemical and fluorescent (bio)sensors and their incorporation in miniaturized detection devices to enhance analytical automation. Other relevant application value-added by the group is the development of more efficient,targeted, spatially and temporally controlled delivery systems to carry multiple molecules for the improvement of their (bio)activity. The use of nanoplatforms as bio-mimetic models to study the complex interactions of drugs, bioactive compounds and/or nanoparticles with lipid cell membranes is another topic of interest. Liposomes, cyclodextrins, micelleplexes, lipid, polymeric, magnetic and gold nanoparticles are tools to produce innovative nanoplatforms with potential application in Nanomedicine, Biomedical Engineering, Biosensing, Functional Foods and Industrial Production.
- Smart materials as sustainable delivery carriers
- Nanostructured platforms as biomimetic models
- Multifunctional (bio)sensors for molecular imaging, targeting and diagnosis
- Multipurpose nanoplatforms as enhanced analytical automation tools
- Functionalized nanoplatforms as delivery systems for food applications
- Targeting for treatment approaches using multifunctional platforms
Multifunctional platforms have been successfully developed as proof-of-concept for treatment approaches reaching pre-clinical trials and some are ready for clinical trials. This has been achieved by a rational design approach, driven by the optimization of the processes in a way to be financially competitive, easily scaled-up and optimized according to the pathophysiological characteristics of the targeted disease and administration route. In this field we have accomplished:
- pH sensitive nanoparticles to improve the treatment of tuberculosis. In vivo results demonstrates that a promising approach was developed and the in vitro data demonstrated an efficient strategy to increase infected macrophages internalization.
- Hybrid nanoparticles to target cancer. Multifunctional nanospheres able to provide a combinatorial therapeutic response through hyperthermia and targeted uptake from colorectal cancer were successfully developed and show in vitro evidences of improved efficacy compared with conventional therapies.
- Multifunctional nanoparticles as theranostic approaches for chronic inflammatory conditions. Promising formulations are in ex-vivo trials using human samples, either with synovial tissue or with skin biopsies to treat rheumatoid arthritis and psoriasis, respectively.
- Multiple lipid nanoparticles: the new generation of lipid nanoparticles
A new type of lipid nanoparticles, the multiple lipid nanoparticles (MLN), was developed. An optimized methodology, based on a quality by design approach, was used. MLN have characteristics between nanostructuredlipid carriers (NLC) and multiple emulsions (W/O/W), but without the outer aqueous phase. MLN present large and multiple aqueous vacuoles, which are achieved without the use of any organic solvents, enabling the incorporation of high amounts of both hydrophilic and lipophilic molecules. As MLN are obtained as a semisolid product, they do not require additional water evaporation or separation steps that are often necessary in most formulations, which simplifies the scale-up of this kind of formulation. The designed MLN are suitable for the delivery of drugs and bioactive compounds, due to their low toxicity and high biocompatibility. Additionally, the administration route can be either topical (as a semisolid), or oral (after resuspension).
- Ready-to-use nanoplatforms to drug discovery and development
Ready-to-use nanoplatforms that enable the study of drug-membrane interactions and cellular uptake mechanisms have been successfully designed and exploited. The outcomes have been revealing an undiscussable relation between the interactions of the drug molecules with membrane lipids and both therapeutic and toxic effects. The validation of these nanoplatforms for drug discovery and development was achieved with the most clinically relevant drugs used in cancer diseases. Particularly, the results regarding the combination of anthracyclines-membrane interplay leads to the idea that, when designing and developing new drugs, the different membrane characteristics should be taken into account. In fact, the different properties of cell membranes can modulate anthracyclines behavior, even conditioning their use depending on the type of cancer. Thereby, these nanoplatforms can and should be incorporated in the preclinical phase of anticancer drugs’ development. They allow to predict the pharmacokinetic properties of novel compounds, to clarify their mechanisms of action and toxicity and allow the selection of the best candidates for in vivo evaluation.
- Novel and miniaturized (bio)assays for (eco)toxicity screening
A generic tool for rapid screening of the (eco)toxicity of chemicals and materials was developed based on a battery of miniaturized (bio)assays, as a part of their sustainable synthesis in the early stage of their development. Molecular and cellular tests are useful to clarify the impact of particular structural elements and to guide their modification to reduce their hazardous potential. The evaluation of toxicity by means of enzymes with important biological functions or whole cell presents additional advantages such as simplicity of laboratory implementation and data interpretation as well as reduction of costs and duration of the assays. With downscaling of conventional procedures in micro conduits, rigorous control of the reaction conditions in terms of time and volumes are attained with advantages regarding assay´s robustness. Thus valuable tools are proposed for the multidimensional assessment of the risk associated to their use.
- Antibiotic-porin interactions an in vitro biophysical study
Biological studies of the uptake of fluoroquinolones and fluoroquinolone-derivatives were performed in several bacterial strains that have a series of porin mutants which lack one or several major outer membrane proteins (OmpF, OmpC, lamB, OmpR). Based on the biological experiments, the in vitro biophysical study of antibiotic-porin interactions using purified porins incorporated into liposomes has been performed. Characterization of the liposome/proteoliposome systems and bacteria, in the presence and absence of compounds, was carried out by fluorescence techniques, light scattering and AFM. Biophysical properties such as fluidity of bacterial membranes has been characterized in a multitude of bacterial strains, from Gram-negatives to Gram-positives, and both susceptible/reference strains and multidrug-resistant clinical isolates, also in the presence and absence of antibiotics. To make the most of the bacterial collection that has been constructed mostly during the last year, antimicrobial susceptibility testing has been performed to assess the potential antimicrobial activity of diverse extracts and compounds, such as antimicrobial peptides and cationic polymers.
- Low-cost ultrasensitive sensors platforms for portable devices
To provide reliable and efficient analytical tools for a variety of health, food and environmental challenges, several electrochemical, surface-enhanced Raman spectroscopic and fluorescent (bio)sensors were successfully developed. The excellent performing characteristics (selectivity, sensitivity, linear working range, precision, accuracy, etc.) and the small size of these sensors will enable their inclusion in portable and/or disposable devices, resulting in cost effective sensing strategies for point-of-care or in situ applications. We have accomplished a low-cost SERS (Surface-enhanced Raman spectroscopy) substrates for point-ofcare portable sensors, using silver nanostars drop-casted on hydrophilic wells patterned on paper, were also implemented. A low limit of detection for rhodamine-6G has been achieved, with good signal uniformity and stability. The optimization of the aqueous synthesis of new fluorescent nanoprobes to prepare gram-amounts of nanomaterials with improved selectivity and surface reactivity, capable of inclusion into portable sensing devices was also achieved. The developed fluorescent nanoprobes were assayed in the determination of various metal ions in distinct samples demonstrating a high efficiency for monitoring Hg(II) levels.