Biology subjects

Harun, A.

Publications and source records attributed to Harun, A..

4 recordsLinked to original sources

bioRxiv2026

Architecture-Dependent Stability, Cellular Uptake, and Redox Modulation of Poly(p-Coumaric Acid) Hybrid Nanoparticles for Ovarian Carcinoma Intervention

The clinical efficacy of fluorescence-guided surgery (FGS) is often compromised by the poor photostability and biologically inert nature of conventional contrast agents such as Indocyanine Green (ICG). While nanocarriers can enhance dye stability, they often function primarily as passive delivery vehicles, requiring additive complexity to achieve therapeutic effects. Here, we report a structure-guided approach to develop self-theranostic hybrid nanoparticles where the polycondensation kinetics of the polymer core, poly(p-coumaric acid) (PCA), serve as a critical design parameter governing nanoparticle assembly and downstream optical and biological performance. By systematically varying the reaction duration, we synthesized PCA variants with distinct polymer growth profiles that influence nanoparticle morphology, ICG encapsulation, and fluorescence stability. The optimized PCA1.5h formulation significantly improved the stability of encapsulated ICG, maintaining robust NIR-I fluorescence under storage and surgical illumination conditions. Beyond acting as a structural scaffold, the PCA matrix retained intrinsic redox-modulating activity, leading to increased reactive oxygen species (ROS) signal generation and reduced viability in multiple ovarian cancer cells. The imaging performance of these nanoparticles was further evaluated using 3D bioprinted intraperitoneal tumor phantoms designed to simulate key optical and spatial features relevant to fluorescence-guided imaging. This work establishes reaction-time-dependent PCA growth profiles as an important formulation parameter for integrating imaging performance and intrinsic biological activity within a simplified hybrid nanomaterial platform. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/717943v3_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@6eab63org.highwire.dtl.DTLVardef@1b6220borg.highwire.dtl.DTLVardef@75010dorg.highwire.dtl.DTLVardef@1982be7_HPS_FORMAT_FIGEXP M_FIG TOC C_FIG

bioengineering↗

bioRxiv2025

Ultrabright NIR-II Nanoprobes for Ex Vivo Bioimaging: Protein Nanoengineering Meets Molecular Engineering

Near-infrared (NIR) fluorescence imaging is a powerful, non-invasive tool for cancer diagnosis, enabling real-time, high-resolution visualization of biological systems. While most probes target the first NIR window (NIR-I, 750-950 nm), recent advances focus on the second window (NIR-II, 1000-1700 nm), which offers deeper tissue penetration and reduced interferences from scattering and autofluorescence. However, many current NIR-II nanoprobes show suboptimal brightness and limited validations in more human-centric models. Here, we present an orthogonal strategy combining molecular engineering, by modulating the amount and position of thiophene moieties in semiconducting polymers (SPs), with protein nanoengineering to develop ultrabright NIR-II imaging probes optimized for ex vivo bioimaging in large animal models. The molecular tuning amplifies the NIR-II fluorescence brightness while screening endogenous proteins as encapsulating matrices to improve colloidal stability and enable active targeting. Molecular docking identified bovine serum albumin as the effective candidate, and the resulting protein-complexed nanoprobes were characterized for size, colloidal stability under physiological conditions, and optical performances. Imaging performances were evaluated using tumor-mimicking phantoms in porcine lungs, simulating cancer surgery, and injected at clinically relevant concentrations into ovine brains and porcine ovaries for microvascular visualization and tissue discrimination, respectively. In all scenarios, our protein-complexed nanoprobes outperformed the FDA-approved clinical dye indocyanine green in signal-to-background ratios. Initial in vitro assays confirmed their hemocompatibility, biocompatibility, and cellular uptake in ovarian adenocarcinoma cells. This integrated approach offers a promising platform for developing next-generation ultrabright NIR-II nanoprobes with improved brightness and stability, advancing the potential for image-guided surgery and future clinical translation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/665782v2_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@c8a20org.highwire.dtl.DTLVardef@1403bedorg.highwire.dtl.DTLVardef@1e474corg.highwire.dtl.DTLVardef@1daed69_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

3D Tumor-Mimicking Phantom Models for Assessing NIR I/II Nanoparticles in Fluorescence-Guided Surgical Interventions

Fluorescence image-guided surgery (FIGS) offers high spatial resolution and real-time feedback but is limited by shallow tissue penetration and autofluorescence from current clinically approved fluorophores. The near-infrared (NIR) spectrum, specifically the NIR-I (700-900 nm) and NIR-II (950-1700 nm), addresses these limitations with deeper tissue penetration and improved signal-to-noise ratios. However, biological barriers and suboptimal optical performance under surgical conditions have hindered the clinical translation of NIR-I/II nanoprobes. In vivo mouse models have shown promise, but these models do not replicate the complex optical scenarios encountered during real-world surgeries. Existing tissue-mimicking phantoms used to evaluate NIR-I/II imaging systems are useful but fall short when assessing nanoprobes in surgical environments. These phantoms often fail to replicate the tumor microenvironment, limiting their predictive assessment. To overcome these challenges, we propose developing tumor-mimicking phantom models (TMPs) that integrate key tumor features, such as tunable tumor cell densities, in vivo-like nanoparticle concentrations, biologically relevant factors (pH, enzymes), replicate light absorption components (hemoglobin), and light scattering components (intralipid). These TMPs enable more clinically relevant assessments of NIR-I/II nanoprobes, including optical tissue penetration profiling, tumor margin delineation, and ex vivo thoracic surgery on porcine lungs. The components of TMPs can be further modulated to closely match the optical profiles of in vivo and ex vivo tumors. Additionally, 3D bioprinting technology facilitates a high-throughput platform for screening nanoprobes under realistic conditions. This approach will identify high-performing NIR-I/II probes with superior surgical utility, bridging the gap between preclinical findings and clinical applications, and ensuring results extend beyond traditional in vivo mouse studies. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=46 SRC="FIGDIR/small/636085v2_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@12b283aorg.highwire.dtl.DTLVardef@5e2dc7org.highwire.dtl.DTLVardef@10f6c36org.highwire.dtl.DTLVardef@189590d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Near-Infrared Afterglow Luminescence Amplification via Albumin Complexation of Semiconducting Polymer Nanoparticles for Surgical Navigation in Ex Vivo Porcine Models

Afterglow imaging, leveraging persistent luminescence following light cessation, has emerged as a promising modality for surgical interventions. However, the scarcity of efficient near-infrared (NIR) responsive afterglow materials, along with their inherently low brightness and lack of cyclic modulation in afterglow emission, has impeded their widespread adoption. Addressing these challenges requires a strategic repurposing of afterglow materials that improve on such limitations. Here, we have developed an afterglow probe, composed of bovine serum albumin (BSA) coated with an afterglow material, a semiconducting polymer dye (PFODBT/SP1), called BSA@SP1 demonstrating a substantial amplification of the afterglow luminescence ([~]3-fold) compared to polymer-lipid coated PFODBT (DSPE-PEG@SP1) under same experimental conditions. This enhancement is believed to be attributed to the electron-rich matrix provided by BSA that immobilizes SP1 and enhances the generation of 1O2 radicals, which improves the afterglow luminescence brightness. Through molecule docking, physicochemical characterization, and optical assessments, we highlight BSA@SP1s superior afterglow properties, cyclic afterglow behavior, long-term colloidal stability, and biocompatibility. Furthermore, we demonstrate superior tissue permeation profiling of afterglow signals of BSA@SP1s compared to fluorescence signals using ex vivo tumor-mimicking phantoms and various porcine tissue types (skin, muscle, and fat). Expanding on this, to showcase BSA@SP1s potential in image-guided surgeries, we implanted tumor-mimicking phantoms within porcine lungs and conducted direct comparisons between fluorescence and afterglow-guided interventions to illustrate the latters superiority. Overall, our study introduces a promising strategy for enhancing current afterglow materials through protein complexation, resulting in both ultrahigh signal-to-background ratios and cyclic afterglow signals.

bioengineering↗