Turbidity diagrams of polyanion/polycation complexes in solution as a potential tool to predict the occurrence of polyelectrolyte multilayer deposition.

Surface functionalization with polyelectrolyte multilayer films (PEM films) has become very popular owing to its simplicity and versatility. However, even if some research is already available, this field of surface chemistry lacks a systematic knowledge of how the polyelectrolyte structure and solution conditions influence the growth of PEM films. In this investigation, we focus on the possible relationship between turbidity of polycation and polyanion mixtures in solution, and the buildup of PEM films made from the same polyelectrolytes in the same physicochemical conditions, namely pH, temperature and ionic strength. It comes out that for six different polycation/polyanion combinations there is a clear correlation between the turbidity evolution of polycation/polyanion complexes with the salt concentration and the evolution of the film deposition with the same parameter. In this investigation, the complexes in solution were prepared in conditions where the ratio between the number of cationic to anionic groups was close to unity. Even if there is a correlation between turbidity in solution and PEM film deposition, we found some exceptions in the low salt concentration regime. This work is an extension of the preliminary works of Cohen Stuart (D. Kovačević et al. Langmuir 18 (2002) 5607-5612) and Sukishvili et al. (S.A. Sukhishvili, E. Kharlampieva and V. Izumrudov, Macromolecules 39 (2006) 8873-8881).journal articleresearch support, non-u.s. gov't2010 Jun 012010 02 21importe

Caractérisation physico-chimique des films multicouches de polyélectrolytes à base de polysaccharides et de polypeptides en vue d'applications dans le domaine des biomatériaux

Les multicouches de poyélectrolytes, systèmes auto-assemblés par adsorptions successives de polycations et de polyanions, ouvrent des perspectives dans le domaine de la fonctionnalisation des biomatériaux. L'objectif du présent travail a concerné le développement d'un biomatériau multistratifié à base de films multicouches et de gels d'alginate. Les exigences de biocompatibilité et de biodégradabilité nous ont orienté vers des multicouches à base de polypeptides et de polysaccharides. Nos travaux s'articulent autour de trois axes principaux : (i) Tout d'abord, nous avons comparé le comportement des complexes en solution afin de comprendre comment ils interviennent lors de la construction des films multicouches. Cette étude suggère la possibilité de prédire, par un simple mélange des deux polyélectrolytes de signes opposés, s'ils sont susceptibles ou non de former un film multicouche sous certaines conditions de force ionique. (ii) Dans un deuxième temps, nous nous sommes intéressés à l'influence du changement de force ionique du surnageant sur le film multicouche PLL/HA préformé. Nous avons montré que l'augmentation ou la diminution de la force ionique induit respectivement un gonflement ou un dégonflement du film, accompagné d'une libération des polyélectrolytes avec l'apparition de cavités dans certains cas. Ces changements de force ionique conduisent à la dissolution du film. (iii) Le troisième volet a consisté à déterminer les meilleures conditions permettant d'élaborer, par la méthode de pulvérisation, un biomatériau multi-stratifié en vue d'application dans le domaine de l'ingénierie tissulaire. Ainsi, des films multicouches à base de polypeptides et de polysaccharides ont été superposés avec des gels d'alginates. Les films multicouches joueraient le rôle de réservoir de principes actifs et les gels d'alginate contiendraient des cellules.Alternated adsorption of polycations and polyanions allows to form self-assembled systems called polyelectrolyte multilayers. They offer new perspectives in the domain of functionalization of biomaterials. The objective of this work was to elaborate a multi-stratified biomaterial based on multilayer films and alginate gels. Polypeptides and polysaccharides were chosen because of their biocompatibility and biodegradability properties. This work was performed in three steps: (i) First, we tried to show a correlation between the polycation-polyanion complexation behaviour in solution (PECs) and the possible buildup of polyelectrolyte multilayer films (PEM) for the same polyelectrolyte system. This will provide a very convenient and predictive tool for experimentalists to explore novel polycation/polyanion combinations for the buildup of PEM films. (ii) Then, we investigated the influence of the ionic strength on the multilayer film architectures. The ionic strength increase or decrease of the contacting solution induce respectively swelling or deswelling of PEMs. This phenomenon is accompanied by polyelectrolyte releases and the formation of holes in certain cases. These variations of ionic strength induce moreover dissolution of the PEMs. (iii) Finally, we elaborated new micro-stratified biomaterials aimed to tissue engineering by the spraying method. We determined the best conditions to obtain such architectures and thus, alternated stacking of PEMs and alginate gels could be performed with PEMs playing the role of active molecules reservoir and alginate gels containing the cells

Caractérisation physico-chimique des films multicouches de polyélectrolytes à base de polysaccharides et de polypeptides en vue d'applications dans le domaine des biomatériaux

Les multicouches de poyélectrolytes, systèmes auto-assemblés par adsorptions successives de polycations et de polyanions, ouvrent des perspectives dans le domaine de la fonctionnalisation des biomatériaux. L objectif du présent travail a concerné le développement d un biomatériau multistratifié à base de films multicouches et de gels d alginate. Les exigences de biocompatibilité et de biodégradabilité nous ont orienté vers des multicouches à base de polypeptides et de polysaccharides. Nos travaux s articulent autour de trois axes principaux : (i) Tout d abord, nous avons comparé le comportement des complexes en solution afin de comprendre comment ils interviennent lors de la construction des films multicouches. Cette étude suggère la possibilité de prédire, par un simple mélange des deux polyélectrolytes de signes opposés, s ils sont susceptibles ou non de former un film multicouche sous certaines conditions de force ionique. (ii) Dans un deuxième temps, nous nous sommes intéressés à l influence du changement de force ionique du surnageant sur le film multicouche PLL/HA préformé. Nous avons montré que l augmentation ou la diminution de la force ionique induit respectivement un gonflement ou un dégonflement du film, accompagné d une libération des polyélectrolytes avec l apparition de cavités dans certains cas. Ces changements de force ionique conduisent à la dissolution du film. (iii) Le troisième volet a consisté à déterminer les meilleures conditions permettant d élaborer, par la méthode de pulvérisation, un biomatériau multi-stratifié en vue d application dans le domaine de l ingénierie tissulaire. Ainsi, des films multicouches à base de polypeptides et de polysaccharides ont été superposés avec des gels d alginates. Les films multicouches joueraient le rôle de réservoir de principes actifs et les gels d alginate contiendraient des cellules.Alternated adsorption of polycations and polyanions allows to form self-assembled systems called polyelectrolyte multilayers. They offer new perspectives in the domain of functionalization of biomaterials. The objective of this work was to elaborate a multi-stratified biomaterial based on multilayer films and alginate gels. Polypeptides and polysaccharides were chosen because of their biocompatibility and biodegradability properties. This work was performed in three steps: (i) First, we tried to show a correlation between the polycation-polyanion complexation behaviour in solution (PECs) and the possible buildup of polyelectrolyte multilayer films (PEM) for the same polyelectrolyte system. This will provide a very convenient and predictive tool for experimentalists to explore novel polycation/polyanion combinations for the buildup of PEM films. (ii) Then, we investigated the influence of the ionic strength on the multilayer film architectures. The ionic strength increase or decrease of the contacting solution induce respectively swelling or deswelling of PEMs. This phenomenon is accompanied by polyelectrolyte releases and the formation of holes in certain cases. These variations of ionic strength induce moreover dissolution of the PEMs. (iii) Finally, we elaborated new micro-stratified biomaterials aimed to tissue engineering by the spraying method. We determined the best conditions to obtain such architectures and thus, alternated stacking of PEMs and alginate gels could be performed with PEMs playing the role of active molecules reservoir and alginate gels containing the cells.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Restoring Anticancer Immune Response by Targeting Tumor-Derived Exosomes With a HSP70 Peptide Aptamer.

BACKGROUND: Exosomes, via heat shock protein 70 (HSP70) expressed in their membrane, are able to interact with the toll-like receptor 2 (TLR2) on myeloid-derived suppressive cells (MDSCs), thereby activating them. METHODS: We analyzed exosomes from mouse (C57Bl/6) and breast, lung, and ovarian cancer patient samples and cultured cancer cells with different approaches, including nanoparticle tracking analysis, biolayer interferometry, FACS, and electron microscopy. Data were analyzed with the Student's t and Mann-Whitney tests. All statistical tests were two-sided. RESULTS: We showed that the A8 peptide aptamer binds to the extracellular domain of membrane HSP70 and used the aptamer to capture HSP70 exosomes from cancer patient samples. The number of HSP70 exosomes was higher in cancer patients than in healthy donors (mean, ng/mL ± SD = 3.5 ± 1.7 vs 0.17 ± 0.11, respectively, P = .004). Accordingly, all cancer cell lines examined abundantly released HSP70 exosomes, whereas "normal" cells did not. HSP70 had higher affinity for A8 than for TLR2; thus, A8 blocked HSP70/TLR2 association and the ability of tumor-derived exosomes to activate MDSCs. Treatment of tumor-bearing C57Bl/6 mice with A8 induced a decrease in the number of MDSCs in the spleen and inhibited tumor progression (n = 6 mice per group). Chemotherapeutic agents such as cisplatin or 5FU increase the amount of HSP70 exosomes, favoring the activation of MDSCs and hampering the development of an antitumor immune response. In contrast, this MDSC activation was not observed if cisplatin or 5FU was combined with A8. As a result, the antitumor effect of the drugs was strongly potentiated. CONCLUSIONS: A8 might be useful for quantifying tumor-derived exosomes and for cancer therapy through MDSC inhibition