Ana Sanchez-Sanchez

Advances in Click Chemistry for Single-Chain Nanoparticle Construction

Single-chain polymeric nanoparticles are artificial folded soft nano-objects of ultra-small size which have recently gained prominence in nanoscience and nanotechnology due to their exceptional and sometimes unique properties. This review focuses on the current state of the investigations of click chemistry techniques for highly-efficient single-chain nanoparticle construction. Additionally, recent progress achieved for the use of well-defined single-chain nanoparticles in some promising fields, such as nanomedicine and catalysis, is highlighted.

Design and Preparation of Single-Chain Nanocarriers Mimicking Disordered Proteins for Combined Delivery of Dermal Bioactive Cargos

Inspired by the multifunctionality of vitamin D-binding protein and the multiple transient-binding behavior of some intrinsically disordered proteins (IDPs), a polymeric platform is designed, prepared, and characterized for combined delivery of dermal protective and anticancer bioactive cargos on the basis of artificial single-chain nano-objects mimicking IDPs. For the first time ever, simultaneous delivery of folic acid or vitamin B9 , and hinokitiol, a relevant natural bioactive compound that exhibits anticancer activity against human malignant melanoma cells, from these multidirectionally self-assembled unimolecular nanocarriers is illustrated.

Efficient Synthesis of Single-Chain Globules Mimicking the Morphology and Polymerase Activity of Metalloenzymes.

Endowing unimolecular soft nanoobjects with biomimetic functions is attracting significant interest in the emerging field of single-chain technology. Inspired by the compartmentalized structure and polymerase activity of metalloenzymes, copper-containing compact nanoglobules have been designed, synthesized, and characterized endowed with metalloenzyme mimicking characteristics toward controlled synthesis of water-soluble polymers and thermoresponsive hydrogels. When compared to metalloenzymes, artificial nanoobjects endowed with metalloenzyme mimicking characteristics offer increased stability against thermal changes and reduced degradability by hydrolytic enzymes.

Poly(3,4-ethylenedioxythiophene) (PEDOT) Derivatives: Innovative Conductive Polymers for Bioelectronics

Poly(3,4-ethylenedioxythiophene)s are the conducting polymers (CP) with the biggest prospects in the field of bioelectronics due to their combination of characteristics (conductivity, stability, transparency and biocompatibility). The gold standard material is the commercially available poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). However, in order to well connect the two fields of biology and electronics, PEDOT:PSS presents some limitations associated with its low (bio)functionality. In this review, we provide an insight into the synthesis and applications of innovative poly(ethylenedioxythiophene)-type materials for bioelectronics. First, we present a detailed analysis of the different synthetic routes to (bio)functional dioxythiophene monomer/polymer derivatives. Second, we focus on the preparation of PEDOT dispersions using different biopolymers and biomolecules as dopants and stabilizers. To finish, we review the applications of innovative PEDOT-type materials such as biocompatible conducting polymer layers, conducting hydrogels, biosensors, selective detachment of cells, scaffolds for tissue engineering, electrodes for electrophysiology, implantable electrodes, stimulation of neuronal cells or pan-bio electronics.

Tuning the Selectivity of Biodegradable Antimicrobial Cationic Polycarbonates by Exchanging the Counter-Anion.

There is a growing interest in modern healthcare to develop systems able to fight antibiotic resistant bacteria. Antimicrobial cationic biodegradable polymers able to mimic antimicrobial peptides have shown to be effective against both Gram-positive and Gram-negative bacteria. In these systems, the hydrophilic-hydrophobic ratio and the cationic charge density play a pivotal role in defining the killing efficiency. Nevertheless, many of these antimicrobial polymers show relatively low selectivity as defined by the relative toxicity to mammalian cells or hemolysis relative to pathogens. In this study, a series of polycarbonates containing pendant quaternary ammoniums are used to understand the role of different counter-anions including chloride, citrate, malonate, benzoate, acetate, lactate and trifluoroacetate, and the antibiotic penicillin on antimicrobial efficacy and selectivity. Interestingly, it is found that in spite of the strong antimicrobial activity of trifluoroacetate and benzoate anions, they prove to be much less hemolytic than chloride anion. It is believed that the proper selection of the anion could enhance the potential of antimicrobial polymers to fight against clinically relevant pathogenic infections, while concurrently mitigating harmful side effects.

Low-Temperature Cross-Linking of PEDOT:PSS Films Using Divinylsulfone

Recent interest in bioelectronics has prompted the exploration of properties of conducting polymer films at the interface with biological milieus. Poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS) from a commercially available source has been used as a model system for these studies. Different cross-linking schemes have been used to stabilize films of this material against delamination and redispersion, but the cost is a decrease in the electrical conductivity and/or additional heat treatment. Here we introduce divinylsulfone (DVS) as a new cross-linker for PEDOT:PSS. Thanks to the higher reactiveness of the vinyl groups of DVS, the cross-linking can be performed at room temperature. In addition, DVS does not reduce electronic conductivity of PEDOT:PSS but rather increases it by acting as a secondary dopant. Cell culture studies show that PEDOT:PSS:DVS films are cytocompatible and support neuroregeneration. As an example, we showed that this material improved the transconductance value and stability of an organic electrochemical transistor (OECT) device. These results open the way for the utilization of DVS as an effective cross-linker for PEDOT:PSS in bioelectronics applications.

Enantioselective Ring-Opening Polymerization of rac-Lactide Dictated by Densely Substituted Amino Acids

Organocatalysis is becoming an important tool in polymer science because of its versatility and specificity. To date a limited number of organic catalysts have demonstrated the ability to promote stereocontrolled polymerizations. In this work we report one of the first examples of chirality transfer from a catalyst to a polymer in the organocatalyzed ring-opening polymerization (ROP) of rac-lactide (rac-LA). We have polymerized rac-LA using the diastereomeric densely substituted amino acids (2S,3R,4S,5S)-1-methyl-4-nitro-3,5-diphenylpyrrolidine-2-carboxylic acid (endo-6) and (2S,3S,4R,5S)-1-methyl-4-nitro-3,5-diphenylpyrrolidine-2-carboxylic acid (exo-6), combined with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a cocatalyst. Both diastereoisomers not only showed the ability to synthesize enriched isotactic polylactide with a Pm higher than 0.90 at room temperature but also were able to preferentially promote the polymerization of one of the isomers (l or d) with respect to the other. Thus, exo-6 preferentially polymerized l-lactide, whereas endo-6 preferred d-lactide as the substrate. Density functional theory calculations were conducted to investigate the origins of this unique stereocontrol in the polymerization, providing mechanistic insight and explaining why the chirality of the catalyst is able to define the stereochemistry of the monomer insertion.

Biodegradable Polycarbonate Iongels for Electrophysiology Measurements

In recent years, gels based on ionic liquids incorporated into polymer matrices, namely iongels, have emerged as long-term contact media for cutaneous electrophysiology. Iongels possess high ionic conductivity and negligible vapor pressure and can be designed on demand. In spite of the extensive efforts devoted to the preparation of biodegradable ionic liquids, the investigations related to the preparation of iongels based on biodegradable polymers remain scarce. In this work, biodegradable polycarbonate-based iongels are prepared by ring-opening polymerization of N-substituted eight ring membered cyclic carbonate monomers in the presence of imidazolium lactate ionic liquid. Our iongels are able to take up 10–30 wt % of ionic liquid and become softer materials by increasing the amount of free ionic liquid. Rheological measurements showed that the cross-over point between the storage modulus G′ and loss modulus G″ occurs at lower angular frequencies when the loading of free ionic liquid increases. These gels are able to take up to 30 wt % of the ionic liquid and the ionic conductivity of these gels increased up to 5 × 10−4 S·cm−1 at 25 °C as the amount of free ionic liquid increased. Additionally, we assess the biodegradation studies of the iongels by immersing them in water. The iongels decrease the impedance with the human skin to levels that are similar to commercial Ag/AgCl electrodes, allowing an accurate physiologic signals recording. The low toxicity and biodegradability of polycarbonate-based iongels make these materials highly attractive for cutaneous electrophysiology applications.