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El cáncer de mama triple negativo (TNBC, por sus siglas en inglés) es una forma agresiva de cáncer de mama que supone entre el 10 y el 20 por ciento de los cánceres de mama diagnosticados. Presenta diversos obstáculos tanto en su diagnóstico como en su tratamiento, lo que exige el desarrollo de nuevas estrategias que mejoren los resultados obtenidos en los pacientes que sufren esta enfermedad. En este sentido, la nanomedicina ha surgido como una prometedora solución para abordar las complejidades de esta agresiva enfermedad. Mediante el desarrollo de sistemas basados en nanopartículas, la nanomedicina ofrece soluciones polifacéticas tanto para la intervención terapéutica como para el diagnóstico por imagen. En el ámbito de la terapia, las nanopartículas sirven como plataformas versátiles para la administración selectiva de fármacos, permitiendo la administración localizada de diferentes tipos de agentes terapéuticos en las zonas tumorales al tiempo que se minimiza la toxicidad sistémica. Al combinarlas, por ejemplo, con fármacos quimioterapéuticos y moléculas diana dirigidas a tumores, las nanopartículas multifuncionales resultantes tienen el potencial de mejorar la eficacia y la seguridad de los tratamiento del TNBC..., Triple negative breast cancer (TNBC) is an aggressive form of breast cancer accounting for 10 to 20 percent of breast cancers diagnoses. It presents several obstacles in both diagnosis and treatment, demanding novel strategies to improve patient outcomes. In this regard, nanomedicine has emerged as a promising frontier in addressing the complexities of this aggressive disease. Through the development of nanoparticle-based systems, nanomedicine offers multifaceted solutions for both therapeutic intervention and diagnostic imaging.Within the realm of therapy, nanoparticles serve as versatile platforms for targeted drug delivery, enabling precise administration of different classes of therapeutic agents to tumor sites while minimizing systemic toxicity. By combining them with, for example, chemotherapeutic drugs and tumor-specific targeting molecules, the resulting multifunctional nanoparticles hold the potential to enhance the efficacy and safety of treatment regimens for TNBC...

The development of effective array biosensorsrelies heavily on careful control of the density of surface-immobilized ligands on the transducing platform. In this paperwe describe the synthesis of new dextran−lipase conjugates foruse in immobilizing low molecular weight haptens onto glassplanar waveguides for immunosensor development. Theconjugates were synthesized by immobilizing bacterial thermoalkalophilic lipases (Geobacillus thermocatenulatuslipase 2,BTL2) on agarose macroporous beads, followed by covalent coupling to dextran networks of variable molecular weight (1500−40000). The chimeras were immobilized via nonspecific hydrophobic interactions onto glass planar waveguides modified with1,1,1,3,3,3-hexamethyldisilazane to obtain highly ordered and homogeneous molecular architectures as confirmed by atomic forcemicroscopy. Microcystin LR (MCLR) was covalently bound to the dextran−BTL2 conjugates. The usefulness of this approach inimmunosensor development was demonstrated by determining amounts of MCLR down to a few picograms per liter with anautomated array biosensor and evanescent wave excitation forfluorescence measurements of attached DyLight649-labeledsecondary antibody. Modifying BTL2 with dextrans of an increased molecular weight (>6000) provided surfaces with anincreased loading capacity that was ascribed to the production of three-dimensional surfaces by the effect of analyte binding deepin the volume, leading to expanded dynamic ranges (0.09−136.56 ng L−1), lower limits of detection (0.007±0.001 ng L−1), andlower IC50values (4.4±0.7 ng L−1). These results confirm the effectiveness of our approach for the development of high-performance biosensing platforms., Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

The straightforward synthesis of novel enzyme–metalNP nanobiohybrids in aqueous medium was developed. These new nanobiohybrids were excellent multivalent catalysts combining both activities in various sets of synthetic reactions even at ultra-low concentrations (ppb amount)., Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

This Communication presents the developmentof a novel strategy for the easy conjugation of biomolecules tohydrophobic magnetic microparticles via reversible coating withpreviously functionalized lipase molecules. First, the ability oflipase to be strongly adsorbed onto hydrophobic surfaces wasexploited for the stabilization of microparticles in aqueousmedium by the creation of a hydrophilic surface. Second, thesurface amino acids of lipase can be tailored to suit biomoleculeconjugation. This approach has been demonstrated by amino-epoxy activation of lipase, enabling the conjugation of differentbiomolecules to the magnetic particle’s surface. For example, itwas possible to immobilize 70% ofEscherichia coliproteins onthe recovered particles. Furthermore, this strategy could beextended to other lipase chemical modification protocols,enablingfine control of biomolecule coupling. These conjugation techniques constitute a modular methodology that also permitsthe recycling of the magnetic carrier following use, Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

Enzyme‐powered micro/nanomotors have myriads of potential applications in various areas. To efficiently reach those applications, it is necessary and critical to understand the fundamental aspects affecting the motion dynamics. Herein, we explored the impact of enzyme orientation on the performance of lipase‐powered nanomotors by tuning the lipase immobilization strategies. The influence of the lipase orientation and lid conformation on substrate binding and catalysis was analyzed using molecular dynamics simulations. Besides, the motion performance indicates that the hydrophobic binding (via OTES) represents the best orienting strategy, providing 48.4 % and 95.4 % increase in diffusion coefficient compared to hydrophilic binding (via APTES) and Brownian motion (no fuel), respectively (with C[triacetin] of 100 mm). This work provides vital evidence for the importance of immobilization strategy and corresponding enzyme orientation for the catalytic activity and in turn, the motion performance of nanomotors, and is thus helpful to future applications., Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

Three biocompatible polymers, polyethylene glycol (PEG), dextran and chitosan, have been used in this work to control the colloidal stability of magnetic nanoparticles (14 ± 5 nm in diameter) and to vary the aggregation state in order to study their effect on relaxometric and heating properties. Two different coating strategies have been deeply developed; one based on the formation of an amide bond between citric acid coated nanoparticles (NPs) and amine groups present on the polymer surface and the other based on the NP encapsulation. Relaxometric properties revealed that proton relaxation rates strongly depend on the coating layer hydrophilicity and the aggregation state of the particles due to the presence of magnetic interactions. Thus, while PEG coating reduces particle aggregation by increasing inter-particle spacing leading to reduction of both T1 and T2 relaxation, dextran and chitosan lead to an increase mainly in T2 values due to the aggregation of particles in bigger clusters where they are in close contact. Dextran and chitosan coated NPs have also shown a remarkable heating effect during the application of an alternating magnetic field. They have proved to be potential candidates as theranostic agents for cancer diagnosis and treatment. Finally, cytotoxicity of PEG conjugated NPs, which seem to be ideal for intravenous administration because of their small hydrodynamic size, was investigated resulting in high cell viability even at 0.2 mg Fe ml−1 after 24 h of incubation. This suspension can be used as drug/biomolecule carrier for in vivo applications., Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

AbstractRhizomucor miehei lipase (RML) is greatly hyperactivated (around 20‐ to 25‐fold toward small substrates) in the presence of sucrose laurate. Hyperactivation appears to be an intramolecular process because it is very similar for soluble enzymes and covalently immobilized derivatives. The hyperactivated enzyme was immobilized (in the presence of sucrose laurate) on cyanogen bromide‐activated Sepharose (very mild covalent immobilization through the amino terminal residue), on glyoxyl Sepharose (intense multipoint covalent immobilization through the region with the highest amount of Lys residues), and on different anion exchangers (by multipoint anionic exchange through the region with the highest density of negative charges). Covalent immobilization does not promote the fixation of the hyperactivated enzyme, but immobilization on Sepharose Q retains the hyperactivated enzyme even in the absence of a detergent. The hydrolysis of fish oils by these hyperactivated enzyme derivatives was sevenfold faster than by covalently immobilized derivatives and three and a half times faster than by the enzyme hyperactivated on octyl‐Sepharose. The open structure of the hyperactivated lipase is fairly exposed to the medium, and no steric hindrance should interfere with the hydrolysis of large substrates. These new hyperactivated derivatives seem to be more suitable for hydrolysis of oils by RML immobilized inside porous supports. In addition, the hyperactivated derivatives are fairly stable against heat and organic cosolvents. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011, Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

The preparation and performance of a suitable chimeric biosensor basedon antibodies (Abs) immobilized on lipase-coated magnetic particles by means of astanding orienting strategy are presented. This novel system is based on hydrophobicmagnetic particles coated with modified lipase molecules able to orient and furtherimmobilize different Abs in a covalent way without any previous site-selective chemicalmodification of biomacromolecules. Different key parameters attending the process werestudied and optimized. The optimal preparation was performed using a controlled loading(1 nmol Ab g−1chimeric support) at pH 9 and a short reaction time to recover abiological activity of about 80%. AFM microscopy was used to study and confirm the Abs-oriented immobilization on lipase-coated magnetic particles and thefinal achievement of ahighly active and recyclable chimeric immune sensor. This direct technique wasdemonstrated to be a powerful alternative to the indirect immunoactivity assay methodsfor the study of biomacromolecule-oriented immobilizations., Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

Biomedical magnetic colloids commonly used in magnetic hyperthermia experiments often display a bidisperse structure, i.e., are composed of stable nanoclusters coexisting with well-dispersed nanoparticles. However, the influence of nanoclusters in the optimization of colloids for heat dissipation is usually excluded. In this work, bidisperse colloids are used to analyze the effect of nanoclustering and long-range magnetic dipolar interaction on the magnetic hyperthermia efficiency. Two kinds of colloids, composed of magnetite cores with mean sizes of around 10 and 18 nm, coated with oleic acid and dispersed in hexane, and coated with meso-2,3-dimercaptosuccinic acid and dispersed in water, were analyzed. Small-angle X-ray scattering was applied to thoroughly characterize nanoparticle structuring. We proved that the magnetic hyperthermia performances of nanoclusters and single nanoparticles are distinctive. Nanoclustering acts to reduce the specific heating efficiency whereas a peak against concentration appears for the well-dispersed component. Our experiments show that the heating efficiency of a magnetic colloid can increase or decrease when dipolar interactions increase and that the colloid concentration, i.e., dipolar interaction, can be used to improve magnetic hyperthermia. We have proven that the power dissipated by an ensemble of dispersed magnetic nanoparticles becomes a nonextensive property as a direct consequence of the long-range nature of dipolar interactions. This knowledge is a key point in selecting the correct dose that has to be injected to achieve the desired outcome in intracellular magnetic hyperthermia therapy., Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub