Scientific publications

Current cancer therapies for solid cancers involve surgery, radiotherapy, and chemotherapy, but challenges such as tumor heterogeneity, drug resistance, and poor drug delivery hinder effective treatment. Nano-oncology, specifically liposomes, shows promise by improving drug delivery through better pharmacokinetics and targeting, minimizing toxicity to healthy tissue. Engineered liposomes can enhance drug delivery, and the development of stimuli-responsive nanoparticles offers more precise control over drug release. This study develops a novel all-in-one drug delivery system, using liposomes functionalized with a modified apolipoprotein E peptide (mApoE) for selectively targeting low-density lipoprotein receptor (LDLR) overexpressed on tumor cells and a matrix metalloproteinase 2 (MMP2)-cleavable lipopeptide. The bi-functional liposomes are loaded with Pimasertib, a MAP/ERK kinase inhibitor (MEK1/2), and show enhanced delivery and effectiveness in reducing melanoma cell viability. Furthermore, these liposomes significantly decrease the growth and invasiveness of melanoma 3D spheroids and reduce the expression of epithelial-to-mesenchymal transition markers. These findings highlight the potential of MMP-sensitive, mApoE-functionalized liposomes as effective drug delivery systems for melanoma treatment, providing a promising approach for sustained drug release and targeted therapy in the tumor microenvironment. Moreover, this approach is promising not only for the treatment of melanoma but also for other types of tumors expressing LDLR and MMPs.

Cellular force sensing and transduction are fundamental processes in development, homeostasis, and disease. To understand how cells detect and integrate mechanical forces, we need non-invasive methods to apply forces at the molecular scale while monitoring cellular responses within physiological contexts. Here, we present a mechanoactuated hydrogel interface that can exert forces on integrin adhesion receptors and allows monitoring of traction force responses in real time. The actuation is achieved by light excitation of a rotary molecular motor presenting an adhesion peptide to bind integrins at the cell membrane and to a hydrogel surface via flexible polymer chains. Illumination results in chain twisting and an applied pulling force on the linked integrin receptors within subcellular illuminated areas. Fluorescent particles in the hydrogel allow parallel quantification of cellular forces by traction force microscopy. With this methodology, we monitored talin recruitment, actin organization, and traction force generation and their reversibility in response to applied forces by the rotary motor-interface. We demonstrate reversible talin recruitment, enhanced F-actin polymerization, and a reduction in cell traction force when force is applied to focal adhesions. This research expands the application of nano machine-based actuation within soft hydrogels and showcases its capabilities.

Electrical double-layer capacitors offer high power density and long cycle life but are limited by moderate energy density. We investigate a strategy to improve their performance using quaternary electrolytes containing two distinct cations and two distinct anions. Our theoretical analysis shows that such electrolytes outperform pure ionic liquids and conventional mixtures sharing a common ion. We validate this approach experimentally using [EMIM][BF4] mixed with lithium salts, characterizing their local structure and electrochemical behavior via NMR, Raman spectroscopy, conductivity measurements, and electrochemical testing. We further demonstrate that the enhancement depends sensitively on electrode microporosity, underscoring the interplay between electrolyte composition and pore structure.

This study investigates the role of microporous carbons and carbonate-based electrolytes in addressing challenges related to polysulfides dissolution and electrolyte compatibility in lithium–sulfur (Li–S) batteries. By employing microporous carbons and varying the sulfur content, we investigate the formation of the cathode-electrolyte interphase (CEI) during the first discharge process. We propose an electrochemical nucleophilic mechanism for the formation of the CEI involving polysulfides and solvent molecules in the confined small pores of the cathode. This interphase, primarily composed of LiF, effectively seals the carbon pores, preventing further solvent intrusion and stabilizing the system. Furthermore, it allows the use of wider pores without compromising the system. Our findings reveal that an increased sulfur content within the micropores enhances cycling stability, contradicting trends observed in ether-based systems. These insights highlight the potential of designing Li–S systems with optimized pore structures and electrolyte compositions to achieve greater stability and capacity retention, marking a significant step forward in the development of practical Li–S batteries.

In this study novel polymeric materials based on chitosan (CS) were synthesized by chemically modifying CS with two bioactive moieties: eugenol and a compound containing a thiazolium group. These modifications aimed to impart antioxidant and antimicrobial properties to the matrix. Additionally, the scaffolds were reinforced with chitin nanowhiskers (Nw) to improve their mechanical strength and stability. Porous three-dimensional scaffolds were fabricated via the freeze-drying process, resulting in highly interconnected pore networks suitable for cell infiltration and nutrient transport. Biological characterization revealed that the incorporation of the two bioactive groups significantly enhanced the antioxidant activity and antimicrobial efficacy against both Gram-positive and Gram-negative bacteria to the scaffolds. Mechanical testing demonstrated that the Nw reinforcement increased scaffold stiffness and resilience without compromising porosity. In vitro biological assays using fibroblasts showed favorable cytocompatibility and promoted sustained cell proliferation over three weeks. Fluorescence microscopy confirmed fibroblast adhesion and morphological adaptation within the scaffold architecture. Additionally, the scaffolds were evaluated for their immunomodulatory effects using macrophage cultures, revealing a balanced immune response with reduced proinflammatory signaling, which is critical for successful integration and reduced fibrosis in vivo. These results indicate that those are promising candidates for tissue engineering and regenerative medicine applications.

A classical approach to reduce the percolation threshold in conductive polymer composites is the so-called volume exclusion. While this method proved to lower filler concentration required to achieve electrical conductivity in solid composites, it remains unexplored for liquid conductive composites such as electrofluids (EFs). We propose the combination of emulsions and conductive particles to create EFs with reduced filler content. Conductive emulsions were prepared based on two immiscible liquids, glycerol and polydimethylsiloxane (PDMS), and carbon black (CB) as the conductive filler. The structural characterization of stable emulsions revealed a selective distribution of CB in the PDMS phase (continuous phase), around glycerol droplets (dispersed phase). This configuration led to a decrease in percolation threshold proving the viability of volume exclusion as strategy in EFs. The combination of the CB network and the glycerol droplets resulted in unpredictable mechanoelectrical properties such as a reduced stiffness scaling compared to CB-electrofluids in the pure solvents and the reduction of a strain thickening behavior with increased filler concentration. We evaluated the role of the CB in the emulsion formation, and its impact on the droplet size and size distribution and concluded that this effect must be synergetic with the creation of a stress-carrying filler network that absorbs the elastic energy from the droplet deformation at large strains.

Discrimination of self from non-self RNA is a critical requirement for any cell to respond to infections and to maintain cellular integrity. We report novel functions for two RNA-dependent RNA polymerases (RDRs) in Paramecium. In RNAinterference (RNAi), RDRs are normally involved in the production of large amounts of secondary small interfering RNAs (siRNAs). To characterize the function of RDRs in context of exogenous RNA recognition, we developed a novel double-stranded RNA (dsRNA) application system using dextran nanoparticles to deliver heteroduplex dsRNA to cells as food particles, mimicking the natural phagosomal entry. Small RNA sequencing allows to dissect siRNAs produced from exogenous RNA or RDR transcripts. Contrary to expectations, our data show that Dicer is unable to directly cleave exogenous dsRNA while two RDRs, RDR1 and RDR2, are required for the initial steps of dsRNA-induced RNAi. Paradoxically, these two RDRs must replicate dsRNA before Dicer cleavage. This system works efficiently also with exogenous single-stranded RNA (ssRNA), although RDR2 is dispensable for ssRNA conversion. The function of RDRs is in contrast to that in animals, plants and fungi and extends the functional diversity of these polymerases as RDR-associated complexes appear to control the entry of food RNA into the RNAi machinery.

Fibrotic capsule formation remains a major barrier in the clinical performance of biomedical implants. Here, we demonstrate that synthetic hydrogels mimicking the mechanical properties of fibrotic tissue trigger stromal cell activation and immune remodeling via focal adhesion kinase (FAK)-mediated mechanotransduction. Using a mechanically tunable poly(ethylene glycol) hydrogel platform and subcutaneous implantation in mice, we show that pharmacological inhibition of FAK activity significantly reduces α-smooth muscle actin (α-SMA)-positive myofibroblast activation, collagen I deposition, and fibrotic capsule thickness in a hydrogel stiffness-dependent manner. Flow cytometry and cytokine profiling revealed that FAK inhibition alters the fibrotic niche by reducing CD163-positive M2c macrophages and significantly downregulating pro-fibrotic cytokines including IL-6, and VEGF, while transiently increasing regulatory T cells and elevating IL-10 levels. Importantly, these changes occurred without parallel increases in canonical pro-inflammatory cytokines, indicating selective modulation rather than global immune suppression or activation. These findings position FAK as a central hub translating mechanical cues into coordinated stromal and immune responses. Targeting FAK mechanotransduction may provide a therapeutic strategy to mitigate foreign body responses and improve implant integration across regenerative applications.

Carbon black (CB)-elastomer composites can serve as low-cost, highly deformable sensor materials. We report on the flow-induced anisotropy of CB-silicone films generated via doctor blade coating. Cured films exhibited larger conductivity perpendicular to the coating direction (R II / R > 1). The piezoresistive sensitivity was 2-3 times larger when stretching perpendicular than parallel to the coating direction, with relative resistance increases of 100–200 %. In contrast, the mechanical stress response to strain was isotropic within the measurement uncertainties. Structural analyses at length scales up to the CB agglomerate level (< 1µm) m) yielded only weak structural anisotropy and excluded alignment of small, primary CB aggregates (<150 nm) in flow direction. Small structural anisotropy apparently suffices to induce significant (piezo-)electric anisotropy. Atomistic molecular dynamics simulations of CB in a viscous medium under strong shear indicate that the CB aggregates have a weak tendency to align with the flow. This generally leads to increased conductivity parallel to the coating R II / R <1. Affine deformation in response to small tensile strain reduces conductivity uniformly. Our results show that shear can induce the formation of electrically anisotropic composites but excludes shear alignment as dominating mechanism. We propose that anisotropy is caused by an interplay of extensional flow and weak alignment in the flow-vorticity plane that varies under tensile strain.

There is a need for new electrochemical energy storage materials that can handle high cycling rates (high power) for rapid charging without compromising high energy density, such as high-power Li-ion batteries (LIBs) and Li-ion capacitors (LICs). Electrically conductive and redox-active two-dimensional (2D) materials, such as transition metal carbides and borides, are promising candidates for these applications. Tailoring in-plane chemically ordered MAB phases (i-MAB) has facilitated the synthesis of their 2D derivatives (i-MBenes), which possess ordered vacancies at the metal sites. The first reported i-MBene paper is Mo4/3B2Tx, which is derived from the parent i-MAB phase (Mo2/3Y1/3)2AlB2 by the selective etching of Al and Y. In this study, we report on the synthesis of 2D Mo4/3B2Tx aerogel and its electrochemical performance as an electrode material for LIBs. Our aerogel exhibits remarkable stability during life-cycling testing at high applied specific currents, maintaining a specific capacity of 260 mAh g−1 even after completing 500 cycles under a high specific current of 2 A g−1. At a moderate specific current of 100 mA g−1, it delivers an energy density of 363 Wh kg−1, while at a high specific current of 2 A g−1, it achieves a specific power of 1300 W kg−1. Complementary density functional theory calculations further reveal that Li preferentially occupies hexagonal Mo sites in Mo4/3B2Tx, supporting the observed stable lithiation behavior and excellent high-rate capability. These results suggest that 2D Mo4/3B2Tx aerogel is a promising candidate for high-power LIBs and LICs.