Evaluation of PEG-b-polycarbonates self-assemblies containing azobenzene or coumarin moieties as nanocarriers using paclitaxel as a model hydrophobic drug.

The work assesses the performance of nanocarriers from amphiphilic block copolymers with functional azobenzene or coumarin moieties for delivery of paclitaxel. Placlitaxel was encapsulated by the nanoprecipitation method. Characterisations were performed by DLS, TEM, Zeta potential and HPLC. Cell viability was investigated in HeLa and Huh-5-2-cell lines. Coumarin-containing polymeric micelles (Dh = 26 ± 2 nm, PDI = 0.28, ζ = ‒22.9 ± 3.6 mV) with 11.2 ± 0.5%w/w drug loading showed enhanced cytotoxicity in HeLa cells (IC50 < 0.02 nM) compared to free paclitaxel (IC50 = 0.17 ± 0.02 nM). Azobenzene-containing polymeric vesicles (Dh = 390 ± 20 nm, PDI = 0.24, ζ = ‒33.2 ± 5.0 mV) with a 6.8 ± 0.4%w/w drug loading showed increased cytotoxicity under 530 nm light (IC50 = 0.0114 ± 0.00033 nM) in HeLa cells due to a stimulated delivery of paclitaxel. Effectivity of these block copolymers as paclitaxel nanovectors and light stimulated release has been demonstrated.

Microfluidic Synthesis of Block Copolymer Micelles: Application as Drug Nanocarriers and as Photothermal Transductors When Loading Pd Nanosheets.

The synthesis of polymeric nanoparticles from a block copolymer based on poly(ethylene glycol) and a polymethacrylate containing the nucleobase analog 2,6-diacylaminopyridine is optimized by microfluidics to obtain homogeneous spherical micelles. Loading and delivery properties are studied using naproxen as a model. The incorporation of a Pd precursor in the polymer organic solution fed into the micromixer allows the preparation of Pd(II) precursor-polymer hybrid systems and the subsequent reduction with CO leads to the in situ synthesis of Pd nanosheets inside of the hydrophobic core of the polymeric micelles. This methodology is highly efficient to yield all polymeric nanoparticles loaded with Pd nanosheets as detected by electron microscopy and energy-dispersive X-ray spectroscopy. The cell viability of these Pd nanosheets-containing polymeric nanoparticles is evaluated using five cell lines, showing a high cytocompatibility at the tested concentrations without detrimental effects in cell membrane and nuclei. Furthermore, the use of these hybrid polymeric nanoparticles as photothermal transductors is evaluated using near infrared as irradiation source as well as its application in photothermal therapy using different cell lines demonstrating a high efficiency in all cell cultures.

Supramolecular Functionalizable Linear-Dendritic Block Copolymers for the Preparation of Nanocarriers by Microfluidics.

Hybrid linear-dendritic block copolymers (LDBCs) having dendrons with a precise number of peripheral groups that are able to supramolecular bind functional moieties are challenging materials as versatile polymeric platforms for the preparation of functional polymeric nanocarriers. PEG2k-b-dxDAP LDBCs that are based on polyethylene glycol (PEG) as hydrophilic blocks and dendrons derived from bis-MPA having 2,6-diacylaminopyridine (DAP) units have been efficiently synthesized by the click coupling of preformed blocks, as was demonstrated by spectroscopic techniques and mass spectrometry. Self-assembly ability was first checked by nanoprecipitation. A reproducible and fast synthesis of aggregates was accomplished by microfluidics optimizing the total flow rate and phase ratio to achieve spherical micelles and/or vesicles depending on dendron generation and experimental parameters. The morphology and size of the self-assemblies were studied by TEM, Cryogenic Transmission Electron Microscopy (cryo-TEM), and Dynamic Light Scattering (DLS). The cytotoxicity of aggregates synthesized by microfluidics and the influence on apoptosis and cell cycle evaluation was studied on four cell lines. The self-assemblies are not cytotoxic at doses below 0.4 mg mL-1. Supramolecular functionalization using thymine derivatives was explored for reversibly cross-linking the hydrophobic blocks. The results open new possibilities for their use as drug nanocarriers with a dynamic cross-linking to improve nanocarrier stability but without hindering disassembly to release molecular cargoes.

Polymeric Self-Assemblies Based on tetra-ortho-Substituted Azobenzene as Visible Light Responsive Nanocarriers.

Most of reported polymeric light-responsive nanocarriers make use of UV light to trigger morphological changes and the subsequent release of encapsulated cargoes. Moving from UV- to visible-responsive units is interesting for the potential biomedical applications of these materials. Herein we report the synthesis by ring opening polymerization (ROP) of a series of amphiphilic diblock copolymers, into which either UV or visible responsive azobenzenes have been introduced via copper(I) catalyzed azide-alkyne cycloaddition (CuAAC). These copolymers are able to self-assemble into spherical micelles or vesicles when dispersed in water. The study of the response of the self-assemblies upon UV (365 nm) or visible (530 or 625 nm) light irradiation has been studied by Transmission Electron Microscopy (TEM), Cryogenic Transmission Electron Microscopy (Cryo-TEM), and Dynamic Light Scattering (DLS) studies. Encapsulation of Nile Red, in micelles and vesicles, and Rhodamine B, in vesicles, and its light-stimulated release has been studied by fluorescence spectroscopy and confocal microscopy. Appreciable morphological changes have been induced with green light, and the subsequent release of encapsulated cargoes upon green light irradiation has been confirmed.

Strategies to Stabilize the Photoinduced Supramolecular Chirality in Azobenzene Liquid Crystalline Polymers.

This paper describes the synthesis, thermal characterization and optical properties of liquid crystalline homopolymers and block copolymers with a repeating unit consisting of two functional units, with at least one of them being an azobenzene. Films of these polymers have been irradiated with circularly polarized light at room temperature, evaluating the intensity of the photoinduced chiral signal and its temporal stability upon storage. The paper also explores two different strategies to restrict the relaxation of the photoinduced order. Firstly, block copolymers have been prepared to confine the photoaddressable segments into nanoscopic domains where relaxation should be restricted. Secondly, an alternative homopolymer has been synthesized where the repeating unit combines two chromophores that can be separately photoaddressed, an azobenzene unit to efficiently photoinduce chirality and a cinnamate to fix the chiral signal by photocrosslinking.

Molecular Recognition via Hydrogen Bonding in Supramolecular Complexes: A Fourier Transform Infrared Spectroscopy Study.

We assess the assembly of supramolecular complexes by hydrogen bonding between azocompounds and a diacylaminopyridine monomer by temperature-dependent Fourier transform infrared spectroscopy (FT-IR) and density functional theory (DFT) calculations. The electronic delocalisation in the supramolecular rings formed by multiple hydrogen bonds stabilises the complexes, which coexist with dimeric species in temperature-dependent equilibria. We show how the application of readily available molecular modelling and spectroscopic techniques can predict the stability of new supramolecular entities coexisting in equilibria, ultimately assessing the success of molecular recognition.

Chiral supramolecular organization from a sheet-like achiral gel: a study of chiral photoinduction.

Chiral photoinduction in a photoresponsive gel based on an achiral 2D architecture with high geometric anisotropy and low roughness has been investigated. Circularly polarized light (CPL) was used as a chiral source and an azobenzene chromophore was employed as a chiral trigger. The chiral photoinduction was studied by evaluating the preferential excitation of enantiomeric conformers of the azobenzene units. Crystallographic data and density functional theory (DFT) calculations show how chirality is transferred to the achiral azomaterials as a result of the combination of chiral photochemistry and supramolecular interactions. This procedure could be applied to predict and estimate chirality transfer from a chiral physical source to a supramolecular organization using different light-responsive units.

A bifunctional amorphous polymer exhibiting equal linear and circular photoinduced birefringences.

The large and reversible photoinduced linear and circular birefringences in azo-compounds are at the basis of the interest in these materials, which are potentially useful for several applications. Since the onset of the linear and circular anisotropies relies on orientational processes, which typically occur on the molecular and supramolecular length scale, respectively, a circular birefringence at least one order of magnitude lower than the linear one is usually observed. Here, the synthesis and characterization of an amorphous polymer with a dimeric repeating unit containing a cyanoazobenzene and a cyanobiphenyl moiety are reported, in which identical optical linear and circular birefringences are induced for proper light dose and ellipticity. A pump-probe technique and an analytical method based on the Stokes-Mueller formalism are used to investigate the photoinduced effects and to evaluate the anisotropies. The peculiar photoresponse of the polymer makes it a good candidate for applications in smart functional devices.

Polarization holograms in a bifunctional amorphous polymer exhibiting equal values of photoinduced linear and circular birefringences.

Light-controlled molecular alignment is a flexible and useful strategy introducing novelty in the fields of mechanics, self-organized structuring, mass transport, optics, and photonics and addressing the development of smart optical devices. Azobenzene-containing polymers are well-known photocontrollable materials with large and reversible photoinduced optical anisotropies. The vectorial holography applied to these materials enables peculiar optical devices whose properties strongly depend on the relative values of the photoinduced birefringences. Here is reported a polarization holographic recording based on the interference of two waves with orthogonal linear polarization on a bifunctional amorphous polymer that, exceptionally, exhibits equal values of linear and circular birefringence. The peculiar photoresponse of the material coupled with the holographic technique demonstrates an optical device capable of decomposing the light into a set of orthogonally polarized linear components. The holographic structures are theoretically described by the Jones matrices method and experimentally investigated.

Responsive linear-dendritic block copolymers.

The combination of dendritic and linear polymeric structures in the same macromolecule opens up new possibilities for the design of block copolymers and for applications of functional polymers that have self-assembly properties. There are three main strategies for the synthesis of linear-dendritic block copolymers (LDBCs) and, in particular, the emergence of click chemistry has made the coupling of preformed blocks one of the most efficient ways of obtaining libraries of LDBCs. In these materials, the periphery of the dendron can be precisely functionalised to obtain functional LDBCs with self-assembly properties of interest in different technological areas. The incorporation of stimuli-responsive moieties gives rise to smart materials that are generally processed as self-assemblies of amphiphilic LDBCs with a morphology that can be controlled by an external stimulus. Particular emphasis is placed on light-responsive LDBCs. Furthermore, a brief review of the biomedical or materials science applications of LDBCs is presented.