Julian Bergueiro

Stimuli-responsive nanogel composites and their application in nanomedicine

Nanogels are nanosized crosslinked polymer networks capable of absorbing large quantities of water. Specifically, smart nanogels are interesting because of their ability to respond to biomedically relevant changes like pH, temperature, etc. In the last few decades, hybrid nanogels or composites have been developed to overcome the ever increasing demand for new materials in this field. In this context, a hybrid refers to nanogels combined with different polymers and/or with nanoparticles such as plasmonic, magnetic, and carbonaceous nanoparticles, among others. Research activities are focused nowadays on using multifunctional hybrid nanogels in nanomedicine, not only as drug carriers but also as imaging and theranostic agents. In this review, we will describe nanogels, particularly in the form of composites or hybrids applied in nanomedicine.

Thermoresponsive Nanodevices in Biomedical Applications

In the last couple of decades several drug carriers have been tailored on the nanometric scale by taking advantage of new stimuli responsive materials. Thermoresponsive polymers in particular have been extensively employed as stimuli-responsive building blocks that in combination with other environmental-responsive materials allowed the birth of smarter systems that can respond to more than one stimulus. Examples that highlight the different polymers for thermally triggered drug delivery will be described. A special emphasis will be given to the description of novel theranostic nanodevices that combine more than one responsive modality in order to create a local hyperthermia that leads to the polymer phase transition and triggered drug release, cell recognition, and/or appearance of an imaging signal.

Engineering thermoresponsive polyether-based nanogels for temperature dependent skin penetration

Highly biocompatible thermoresponsive nanogels (tNGs) based on oligo ethylene glycol (OEG) as thermoresponsive unit and dendritic polyglycerol (dPG) as cross-linker, were precisely engineered in terms of size and volume phase transition temperature (VPTT). Preliminary uptake studies into human skin were realized to show the temperature-dependent internalization behavior of these systems.

Near Infrared Dye Conjugated Nanogels for Combined Photodynamic and Photothermal Therapies

There is a need for new and smart formulations that will help overcome the limitations of organic dyes used in photodynamic (PDT) and photothermal (PTT) therapy and significantly accelerate their clinical translation. Therefore the aim of this work was to create a responsive nanogel scaffold as a smart vehicle for dye administration. We developed a methodology that enables the conjugation of organic dyes to thermoresponsive nanogels and yields biocompatible, nanometer-sized products with low polydispersity. The potential of the dye-nanogel conjugate as a photothermal and photodynamic agent has been demonstrated by an in vitro evaluation with a model human carcinoma cell line. Additionally, confocal cell images showed their cellular uptake profile and their potential for bioimaging and intracellular drug delivery. These conjugates are a promising scaffold as a theranostic agents and will enable further applications in combination with controlled drug release.

Unexpected Chiro-Thermoresponsive Behavior of Helical Poly(phenylacetylene)s Bearing Elastin-Based Side-Chains

The thermoresponsive behavior of an elastin-based polymer can be altered by the polymeric macromolecular conformation. Thus, when the elastin basic amino acid sequence VPGVG is used as a pendant group of a poly(phenylacetylene) (PPA) its thermoresponsive behavior in water can be remotely detected through conformational changes on the formed helix. Circular dichroism at different temperatures shows an inversion of the first Cotton effect (450 nm) at 25.8 °C that matches with the cloud point temperature. The elastin-based side-chain poly(phenylacetylene) shows an upper critical solution temperature with low pH and concentration dependency, not expected in elastin-based polymers. It was found that the polymer self-assembles in water into spherical nanoparticles with hydrodynamic diameters of 140 nm at the hydrophobic state.

Optimizing Circulating Tumor Cells’ Capture Efficiency of Magnetic Nanogels by Transferrin Decoration

Magnetic nanogels (MNGs) are designed to have all the required features for their use as highly efficient trapping materials in the challenging task of selectively capturing circulating tumor cells (CTCs) from the bloodstream. Advantageously, the discrimination of CTCs from hematological cells, which is a key factor in the capturing process, can be optimized by finely tuning the polymers used to link the targeting moiety to the MNG. We describe herein the relationship between the capturing efficiency of CTCs with overexpressed transferrin receptors and the different strategies on the polymer used as linker to decorate these MNGs with transferrin (Tf). Heterobifunctional polyethylene glycol (PEG) linkers with different molecular weights were coupled to Tf in different ratios. Optimal values over 80% CTC capture efficiency were obtained when 3 PEG linkers with a length of 8 ethylene glycol (EG) units were used, which reveals the important role of the linker in the design of a CTC-sorting system.