Self-assembled polymeric vectors mixtures: characterization of the polymorphism and existence of synergistic effects in photodynamic therapy

The objective of this work was to assess the relation between the purity of polymeric self-assemblies vectors solution and their photodynamic therapeutic efficiency. For this, several amphiphilic block copolymers of poly(ethyleneoxide-b-ε-caprolactone) have been used to form self-assemblies with different morphologies (micelles, worm-like micelles or vesicles). In a first step, controlled mixtures of preformed micelles and vesicles have been characterized both by dynamic light scattering and asymmetrical flow field flow fractionation (AsFlFFF). For this, a custom-made program, STORMS, was developed to analyze DLS data in a thorough manner by providing a large set of fitting parameters. This showed that DLS only sensed the larger vesicles when the micelles/vesicles ratio was 80/20 w/w. On the other hand, AsFlFFF allowed clear detection of the presence of micelles when this same ratio was as low as 10/90. Subsequently, the photodynamic therapy efficiency of various controlled mixtures was assessed using multicellular spheroids when a photosensitizer, pheophorbide a, was encapsulated in the polymer self-assemblies. Some mixtures were shown to be as efficient as monomorphous systems. In some cases, mixtures were found to exhibit a higher PDT efficiency compared to the individual nano-objects, revealing a synergistic effect for the efficient delivery of the photosensitizer. Polymorphous vectors can therefore be superior in therapeutic applications

Polymeric self-assemblies for photodynamic therapy: A critical approach

The work presented here suggests a new approach in the critical development of polymeric nanovectors for photodynamic therapy (PDT) against cancer. Whereas hundreds of studies quickly jump forward from formation of self-assemblies to biological application without having a thorough examination of the vector solution, we suggest having a parallel assessment of formation/characterization of the nanovectors and biological activity [1]. This is possible by first using a careful physical chemistry characterization of the vectors by both batch techniques (light and neutron scattering, electron microscopy, atomic force microscopy) and Asymmetrical Flow Field-Flow Fractionation (AsFlFFF) coupled to adequate detectors (refractometry, light scattering) [2]. This enables us to fully characterize the vectors regarding purity, size and zeta potential

Crosslinked polymeric self-assemblies as an efficient strategy for photodynamic therapy on a 3D cell culture

In order to compare the efficiency of crosslinked nano-vectors in the field of photodynamic therapy (PDT) both on 2D and 3D cell cultures, various polymeric crosslinked self-assemblies based on poly(ethyleneoxide-b-ε-caprolactone) have been synthesized by radical polymerization of acrylate end-functionalized polymers. Crosslinked self-assemblies obtained from the reaction of the functionalized polymers with ethyleneglycoldimethacrylate (EGDMA) were compared to chain-end polymerized and to unreacted ones. Polymeric micelles with a size between 10 and 20 nm were obtained, as well as an elongated system with a length close to 100 nm. They all have been characterized by Transmission Electron Microscopy and Dynamic Light Scattering but also by Asymmetrical Flow Field-Flow Fractionation in order to prove that they consisted of pure self-assemblies. Chain-end polymerization or crosslinking did not induce any change in morphology nor strong size modification. After post-encapsulation of a photosensitizer, namely Pheophorbide a, the systems have been examined for their potential use in PDT on HCT-116 and FaDu human tumor cell lines both in 2D and 3D cultures. The crosslinked vectors were observed to be the most efficient on both cell lines cultivated in 3D spheroids, whereas unreacted or chain-end polymerized ones presented a lower activity. This was different from the trend observed in 2D cell cultures where an uncrosslinked micelle was observed to be efficient at a lower concentration compared to its chain-end polymerized or crosslinked analogue. The different synthesized self-assemblies also allowed assessing the influence of polymer chain length and shape on PDT efficiency. The molecular weight of the polymer did not lead in our case to efficiency change, for similar size and surface characteristics. As for the shape effect, the elongated self-assembly was not observed in our case to be more efficient than spherical micelles. Crosslinked polymeric vectors are therefore promising vectors for 3D tumor treatment

Terahertz Time-Domain Spectroscopy of Thermoresponsive Polymers in Aqueous Solution

The behavior of highly concentrated aqueous solutions of two thermoresponsive polymers poly(N-isopropylacrylamide) (PNIPAm) and poly(N-vinylcaprolactam) (PVCL) have been investigated by terahertz time-domain spectroscopy (THz-TDS). Measurements have been performed for concentrations up to 20 wt %, over a frequency range from 0.3 to 1.5 THz and for temperatures from 20 to 45 °C including the zone for lower critical solution temperature (LCST). THz-TDS enables the study of the behavior of water present in the solution (i.e., free or bound to the polymer). From these measurements, in addition to phase transition temperature, thermodynamic data such as variation of enthalpy and entropy can be inferred. Thanks to these data, further insights upon the mechanism involved during the dehydration phenomenon were obtained. These results were compared to the ones issued from dynamic light scattering, spectroscopy, or microscopy techniques to underline the interest to use THz-TDS as a powerful tool to characterize the behavior of thermoresponsive polymers in highly concentrated solutions

Catalyseurs tensio-actifs pour réaction de métathèse en solution micellaire non dégazée

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Asymmetrical flow field-flow fractionation with multi-angle light scattering and quasi elastic light scattering for characterization of poly(ethyleneglycol-b-ɛ-caprolactone) block copolymer self-assemblies used as drug carriers for photodynamic therapy

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Use of hyperbranched polymers to form and stabilize metal nanoparticules in water

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