Biology subjects

Ronzier, E.

Publications and source records attributed to Ronzier, E..

4 recordsLinked to original sources

bioRxiv2026

Direct Synthesis of Targeted Nanosized ICG J-aggregate for Photoacoustic Imaging

Indocyanine green (ICG) J-aggregates (JAs) are self-assembled particles characterized by a sharp and strong absorption peak in the near-infrared region ([~]890 nm), enhanced photostability, low fluorescence, and high photothermal conversion efficiency, compared to monomeric ICG. These attributes make ICG-JAs promising contrast agent candidates for photoacoustic imaging (PAI). However, traditional methods for synthesizing ICG-JAs often yield particles without targeting ability, which limit their applications. Thus, to synthesize targeted nanoscale JA, complex and multi-step encapsulation and filtration processes are generally required. To solve this issue, we introduce a robust and rapid strategy for direct synthesis of targeted nanoscale ICG-JA by co-assembling ICG and ICG-azide dyes under optimized formulation conditions that do not require encapsulation. The resulting nanoscale JAAZ particles (nJAAZ) exhibit diameters of [~]120-150 nm and are amenable to direct bio-orthogonal functionalization via copper-free click chemistry for the attachment of virtually any targeting ligands and/or biomolecules. We further demonstrate the strong photoacoustic signal generation of these nJAAZ in vitro and in vivo, highlighting their potential as a modular high-performance contrast agent platform for PAI. This work establishes a scalable and tunable platform for engineering functional JAs, opening new avenues for targeted molecular imaging and theranostic applications.

bioengineering↗

bioRxiv2026

Computational and Proteomic Analyses Reveal Cardiac Dysfunction and Heart Failure-Associated Biomarker Secretion from Venezuelan Equine Encephalitis Virus TC83-infected human IPSC-derived Cardiomyocytes

Arthropod-borne pathogens, many of which are neurotropic, can disseminate beyond the central nervous system to infect peripheral organs. In recent years, an increasing number of cardiac dysfunctions have been reported following arthropod-borne viral infections; however, the mechanism underlying these cardiac manifestations remains poorly understood. In this study, we investigated the impact of Venezuelan Equine Encephalitis Virus (VEEV) TC-83 infection on cardiac function and immune-response of human induced-pluripotent stem cell (hIPSC)-derived cardiomyocytes (hIPSC-CMs). We first confirmed the successful differentiation of hIPSCs into spontaneously beating hIPSC-CMs. We then demonstrated that these cells are highly susceptible to VEEV TC-83 infection, which induced pronounced arrhythmias and complete cessation of beating within 24 hours post-infection. To quantify these functional changes, we developed a segmentation-free computational pipeline that converts frame-to-frame motion in brightfield time-lapse movies into a one-dimensional signal reflecting contractile activity and extracts beat timing, beat rate, and rhythm-regularity features in the time and frequency domains. This analysis revealed progressive disruption of beating dynamics following VEEV TC-83 infection, with early rhythm instability and complete loss of coordinated beating by 24 hours post-infection. Furthermore, mass spectrometry analysis of VEEV TC-83-infected hIPSC-CMs supernatants revealed the presence of biomarkers typically associated with heart failure in patients, underscoring a virus-induced cardiac functional impairment. Together, these findings provide new insight into cardiac complications associated with arthropod-borne viral infections and may support advances in preventive medicine.

cell biology↗

bioRxiv2025

Synthesis and Characterization of ICG-based Near-infrared Photoacoustic Contrast Agents

Near-infrared photoacoustic imaging (NIR-PAI) integrates optical excitation with ultrasound detection to enable high-resolution, deep-tissue imaging by taking advantage of reduced light scattering and absorption in this spectral window. Despite its potential, clinical translation of contrast-enhanced NIR-PAI is limited by the scarcity of effective contrast agents. Indocyanine green (ICG), an FDA-approved NIR dye, is a strong candidate due to its biocompatibility and photoacoustic efficiency. However, its concentration-dependent aggregation, lack of facile targeting strategies, instability in aqueous environments, and low photostability result in variable signal, high background noise, and reduced reliability in vivo. To address these challenges, we developed three biocompatible ICG-based nanoprobe platforms amenable to facile, scalable synthesis: 5-arm DNA-ICG nanostructures (5-arm DNA-ICG), lipid-shelled ICG nanobubbles (ICG-NBs), and Azide-modified ICG J-aggregates (JAAZ). These platforms are designed to preserve ICG monomers or control aggregation, enabling enhanced NIR-PAI performance. Spectroscopic and photoacoustic analyses revealed consistent absorbance and photoacoustic profiles, showing enhanced signals compared to free ICG. The greatest improvement was observed for JAAZ, followed by ICG-NBs and 5-arm DNA-ICG. Photostability studies showed that JAAZ aggregation protects ICG from light-induced photodegradation, whereas monomer preservation in 5-arm DNA-ICG and ICG-NBs provides less protection and moderate signal stability. All three probes demonstrated stable performance under physiological conditions, achieved strong signal-to-noise ratios at depth and under tissue-mimicking conditions, and required markedly reduced probe concentrations to generate robust signals. Their modular architectures allow incorporation of targeting ligands, offering molecular specificity and multimodal functionality. Collectively, these contrast agent platforms provide noninvasive, deep-tissue molecular imaging and biosensing, with strong potential for future preclinical and clinical translation, and represent a promising alternative to free ICG for biomedical applications.

bioengineering↗

bioRxiv2024

The p24-family member, TMED9, clears misfolded GPI-anchored proteins from theER to the Golgi via the Rapid ER Stress-Induced Export pathway

The p24-family member, TMED9, has recently emerged as a player in secretory pathway protein quality control (PQC) that influences the trafficking and degradation of misfolded proteins. Here we show that TMED9 plays a central role in the PQC of GPI-anchored proteins (GPI-APs). Typically, upon release from the endoplasmic reticulum (ER)-resident chaperone calnexin, misfolded GPI-APs traffic to the Golgi by an ER-export pathway called Rapid ER stress-induced Export (RESET). From the Golgi, they access the plasma membrane where they are rapidly internalized for lysosomal degradation. We used biochemical and imaging approaches in cultured cells to demonstrate that at steady-state, the majority of misfolded GPI-APs reside in the ER in association with calnexin and TMED9. During RESET, they dissociate from calnexin and increase their association with TMED9. Inhibition of TMED9s function through siRNA-induced depletion or chemical inhibitor, BRD4780, blocked ER-export of misfolded GPI-APs. By contrast, TMED9-inhibition did not prevent ER-export of wild type GPI-APs, indicating a specific role for TMED9 in GPI-AP PQC. Intriguingly, we discovered that acute treatment with BRD4780 induced a shift in TMED9 localization away from the ER to the downstream Golgi cisternae and blocked the RESET pathway. Upon removal of BRD4780 following acute treatment, TMED9 regained access to the ER where TMED9 was able to associate with the RESET substrate and restore the RESET pathway. These results suggest that TMED9 plays a requisite role in RESET by capturing misfolded GPI-APs that are released by calnexin within the ER and conveying them to the Golgi.

cell biology↗