Publications

Smart materials have emerged as a promising innovation in cancer treatment, offering targeted, controlled, and efficient therapeutic strategies that minimize side effects and improve patient outcomes. This review explores the development and application of various smart materials in cancer therapy, such as pH-sensitive and redox-responsive hydrogels, designed to respond to the unique conditions within the tumor microenvironment (TME), and near-infrared sensitive and electroresponsive systems (including the subfield of piezoelectric materials) that respond to exogenous stimuli, also including multiresponsive materials systems. These materials enable precise drug delivery, enhance the efficacy of traditional therapies, and integrate diagnostic capabilities, fostering the advancement of theragnostic approaches. Despite significant progress, challenges persist, impairing the clinical translation of these technologies. Future perspectives emphasize the need for interdisciplinary collaboration, the development of standardized evaluation protocols, and the integration of emerging technologies, like artificial intelligence (AI), to overcome these challenges. Despite significant progress, these approaches face important limitations, including heterogeneity of TMEs, variability in stimuli-responsiveness, and concerns regarding long-term biocompatibility and large-scale production. Clinical translation also remains limited, with only a few polymeric or nanoparticle-based systems advancing to trials, while more complex multiresponsive and electroresponsive platforms remain at proof-of-concept stage. Future perspectives emphasize the need for standardized evaluation protocols, scalable manufacturing, and integration with emerging technologies such as AI to accelerate safe and effective translation into clinical practice.

JTD Keywords: Cancer, Chitosan, Doxorubicin, Drug-delivery, Electroresponsive, Hydrogel, Micelles, Nanogels, Nanoparticles, Ph, Ph-responsive delivery, Piezoelectric, Redox, Release, Smart materials, Target

In recent years, enzyme-powered nanomotors (NMs) have emerged as promising tools for biomedical applications. They exhibit active motion in complex media, whereas traditional passive nanoparticles (NPs) typically remain trapped. Despite their potential, nanogels (NGs)-3D, cross-linked polymeric networks with high water retention and environmental responsiveness-remain underexplored as cores for enzymatic NMs. Here, fine-tuned NGs designed to confer smart properties are presented, allowing them to adapt their size and density in response to external stimuli (e.g., pH, temperature, and redox conditions). After anchoring urease to these NGs to produce nanogel-nanomotors (NGs-NMs), they exhibited both individual and collective motion at a very low urea concentration, enabling displacement in highly viscous environments. To achieve this, four NGs formulations based on p-(N-isopropylacrylamide) co-polymerized with p-Itaconic acid (p-(NIPAM-co-IAc)) are developed, cross-linked with either N,N '-methylenebisacrylamide (BIS) and/or N,N '-bis(acryloyl)cystamine (BAC), and coated with p-(2-hydroxyethyl methacrylate) (p-HEMA). This results, obtained via confocal microscopy and flow cytometry, demonstrate their rapid cell internalization. Moreover, synchrotron-based infrared spectroscopy (SR-FTIRM) allowed to demonstrate that NGs-NMs can tune the physicochemical composition of tumoral cells. This findings underscore the potential of NGs-NMs, combining adaptability, safety, and efficacy. They represent the evolution in NMs technology, paving the way for groundbreaking advancements in personalized medicine.

JTD Keywords: Active mater, Enzymatic nanomotors, Hydrogels, Nanobots, Nanogels, Poly(2-hydroxyethyl methacrylate), Ure, Viscous medi

Bacterial infections pose a significant global health challenge aggravated by the rise of antimicrobial resistance (AMR). Among the obstacles preventing effective treatment are biological barriers (BBs) within the body such as the mucus layer. These BBs trap antimicrobials, necessitating higher doses and ultimately accelerating AMR. Addressing this issue requires innovative therapeutic strategies capable of bypassing BBs to deliver drugs more effectively. Here, we present nanomotors (NMs) based on hyaluronic acid (HA)- and urease-nanogels (NGs) as a solution to navigate effectively in viscous media by catalyzing the decomposition of urea into ammonium and carbon dioxide. These HA-based nanomotors (HA-NMs) were loaded with chloramphenicol (CHL) antibiotic and demonstrated superior antimicrobial activity against Escherichia coli(E. coli) compared to mesoporous silica NMs (MSNP-NMs), a reference in the field of NMs. Moreover, using an in vitro transwell model we evaluated the ability of HA-NMs to penetrate mucin barriers, effectively reducing E. coli proliferation, whereas the free antibiotic did not reduce bacteria proliferation. The optical density reduction at 24 h was over ten times greater than with free CHL. These organic-based enzyme-powered NMs represent a significant advancement in drug delivery, offering a promising approach to combat AMR while addressing the challenges of crossing complex BBs.

JTD Keywords: Bacterial infections, Biologicalbarriers, Design, Drug deliver, Enzyme, Mucu, Nanogels, Nanomotors, Nanoparticles

Innovative insulin delivery systems contemplate combining multi-pharmacokinetic profiles for glycemic control. Two device configurations have been designed for the controlled release of insulin using the same chemical compounds. The first insulin delivery system, which displays a rapid release response that, in addition, is enhanced on a short time scale by electrical stimulation, consists on an insulin layer sandwiched between a conducting poly(3,4-ethylenedioxythiophene) (PEDOT) film and a poly-gamma-glutamic acid (gamma-PGA) hydrogel. The second system is constituted by gamma-PGA hydrogel loaded with insulin and PEDOT nanoparticles by in situ gelation. In this case, the insulin release, which only starts after the degradation of the hydrogel over time (i.e. on a long time scale), is slow and sustained. The combination of an on-demand and fast release profile with a sustained and slow profile, which act on different time scales, would result in a very efficient regulation of diabetes therapy in comparison to current systems, allowing to control both fast and sustained glycemic events. Considering that the two systems developed in this work are based on the same chemical components, future work will be focused on the combination of the two kinetic profiles by re-engineering a unique insulin release device using gamma-PGA, PEDOT and insulin.

JTD Keywords: Conducting polymer, Constant, Diabetes, Diabetes-mellitus, Drug-delivery, Electrodes, Electrostimulation, Glucose-responsive hydrogels, Hydrogel, Molecular dynamics, Molecular-dynamics, Nanogels, Nanoparticles, Poly(3,4-ethylenedioxythiophene), Risk

© 2020 Elsevier B.V. Semi-interpenetrated nanogels (NGs) able to release and sense diclofenac (DIC) have been designed to act as photothermal agents with the possibility to ablate cancer cells using mild-temperatures (<45 °C). Combining mild heat treatments with simultaneous chemotherapy appears as a very promising therapeutic strategy to avoid heat resistance or damaging the surrounding tissues. Particularly, NGs consisted on a poly(N-isopropylacrylamide) (PNIPAM) and dendritic polyglycerol (dPG) mesh containing a semi-interpenetrating network (SIPN) of poly(hydroxymethyl 3,4-ethylenedioxythiophene) (PHMeEDOT). The PHMeEDOT acted as photothermal and conducting agent, while PNIPAM-dPG NG provided thermoresponsivity and acted as stabilizer. We studied how semi-interpenetration modified the physicochemical characteristics of the thermoresponsive SIPN NGs and selected the best condition to generate a multifunctional photothermal agent. The thermoswitchable conductiveness of the multifunctional NGs and the redox activity of DIC could be utilized for its electrochemical detection. Besides, as proof of the therapeutic concept, we investigated the combinatorial effect of photothermal therapy (PTT) and DIC treatment using the HeLa cancer cell line in vitro. Within 15 min NIR irradiation without surpassing 45 °C we were able to kill 95% of the cells, demonstrating the potential of SIPN NGs as drug carriers, sensors and agents for mild PTT.

JTD Keywords: cells, cellulose, conducting polymers, controlled delivery, diclofenac, efficiency, electrochemical oxidation, electrochemical sensors, nanogels, nanoparticles, photothermal therapy, pnipam, poly(3,4-ethylenedioxythiophene), Conducting polymers, Electrochemical sensors, Nanogels, Photothermal therapy