bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.02.08.704660

Mesoscopic Fluorescence Imaging of Light-Triggered Chemotherapeutic Release in Cancer Spheroid Models

Kluiszo, E.·Ahmmed, R.·Aliu, B.·Sunar, S. A.·Willadsen, M.·Kutscher, H.·Lovell, J.·Sunar, U.
View original source ↗Export metadata ↓

Abstract

Peritoneal micrometastases (micromets) remain a major barrier to durable cytoreduction in ovarian and other intra-abdominal cancers, because lesions can be difficult to visualize and are often resistant to systemic therapy. Liposomal doxorubicin (Dox) improves pharmacokinetics but can be limited by slow intratumoral release. Porphyrin-phospholipid (PoP) liposomes enable near-infrared light-triggered release of Dox (chemophototherapy (CPT)), creating an opportunity for intraoperative, fluorescence-guided treatment planning and monitoring. Here, we evaluate a laparoscopic fluorescence imaging platform for quantifying light-triggered drug delivery in 2D monolayers and 3D spheroid cluster models. Dox fluorescence increased linearly with administered LC-Dox-PoP concentration in both SCC2095sc and SKOV-3 cultures (R2 = 0.97-0.98 in 2D; R2 = 0.98 in spheroid clusters over 1-9 {micro}g/mL). Laparoscope-derived fluorescence measurements agreed with standard well-plate reader measurements (R2 = 0.89-0.96). Porphyrin fluorescence provided stronger, complementary contrast for localizing spheroid constructs and decreased after activation light exposure, consistent with photobleaching during triggered release. Together, these results support a quantitative imaging framework for fluorescence-guided monitoring of light-triggered liposomal drug release, with potential to inform individualized CPT dosimetry for peritoneal micrometastases. These findings in SCC2095sc (oral squamous cell carcinoma) additionally suggest relevance of fluorescence-guided CPT for head and neck/oral cancer, where localized post-resection adjuvant treatment may improve control of residual disease.

Source connections

Explore related subjects

bioengineeringPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kluiszo, E., Ahmmed, R., Aliu, B., Sunar, S. A., Willadsen, M., Kutscher, H., Lovell, J., Sunar, U.. 2026-02-10. Mesoscopic Fluorescence Imaging of Light-Triggered Chemotherapeutic Release in Cancer Spheroid Models. https://doi.org/10.64898/2026.02.08.704660

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Surfactant-Assisted Colorimetric Signal Enhancement in Paper-Based Glucose Sensing

Paper-based colorimetric sensors offer a low-cost and accessible platform for point-of-care (POC) analysis, but enzyme activity loss during coating and drying can weaken analytical signals and require high enzyme loadings or complex immobilization procedures. Although surfactants are widely used to improve wettability in paper-based assays, their potential contribution to colorimetric performance beyond these effects remains unclear. Here, we investigated surfactant-assisted colorimetric signal enhancement in a glucose assay implemented on a 96-puddle paper plate (96-PPP) and identified Tween 20 as the most effective surfactant. Its effect on detection performance became more pronounced as glucose oxidase (GOx) loading decreased; at 0.1 mg/mL GOx, Tween 20 lowered the limit of detection (LoD) from 0.113 to 0.034 mg/mL (approximately 3.3-fold) over a working range of 0-5 mg/mL, despite no statistically significant change in the measured contact angle at this loading. Tween 20 had no appreciable effect on the reaction in solution but preserved 95% of the apparent reaction rate constant after drying, compared with 11% without it, and atomic force microscopy (AFM) revealed a more dispersed dried enzyme morphology on mica. Tween 20-containing sensors also showed slower signal decay during repeated wetting-drying cycles and thermal stress, retained 77% (vs 26%) of the response at 400 mM NaCl, and exhibited within-PPP and between-batch coefficients of variation (CVs) below 10% (vs 12.3-19.5%), while maintaining glucose selectivity over potentially interfering molecules. These results indicate that Tween 20 enhances paper-based glucose sensing beyond wettability, in part by retaining enzyme cascade activity during drying, although the contributions of the individual enzymes and the underlying mechanism remain to be established.

bioengineering↗
bioRxiv2026

Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx

The dense glycocalyx of cancer cells can restrict immune-cell access to surface antigens and limit CAR-T cell activity. Here, we show that mucin density and epitope position determine how glycocalyx remodeling affects CAR-T cell recognition and killing. We identify KLK5 as a human protease that cleaves tumor-associated mucins, increases access to membrane-proximal antigens, and enhances CAR-T cell function. We then engineer CAR-T cells to display or secrete KLK5, enabling remodeling of the tumor glycocalyx during antigen recognition. KLK5-engineered CAR-T cells improved tumor control across multiple xenograft models, and KLK5-secreting MUC17 CAR-T cells produced the strongest in vivo benefit, prolonging survival compared with conventional MUC17 CAR-T cells. These findings show that CAR-T cells can be engineered to breach the mucin-rich glycocalyx while preserving accessible target epitopes.

bioengineering↗
bioRxiv2026

Wall stiffening is a primary contributor to motility loss in Crohn's disease: an electromechanical modeling study

Fibrotic strictures are among the most disabling complications of Crohn's disease, permanently narrowing the bowel and impairing motility, yet no approved therapy reverses them. Chronic inflammation alters pacemaker-network coupling, smooth-muscle excitability, and calcium-dependent contractility, while fibrosis thickens the bowel wall, narrows the lumen, and changes tissue mechanics. The relative contributions of these coupled electrical, contractile, and structural alterations to motility loss remain unclear. To address this gap, we develop an integrated electromechanical finite-element framework for fibrostenosing Crohn's disease that couples a fibrosis-driven growth model with a FitzHugh-Nagumo electromechanical model. A full-factorial 25 design of experiments is used to quantify the relative effects of electrical diffusivity, excitation threshold, peak active stress, wall stiffness, and hypertrophic remodeling on cyclic lumen-volume deformation. Motility is quantified by the standard deviation of lumen volume over one contraction cycle. Within the parameter ranges examined, increased wall stiffness emerged as the dominant contributor to motility loss, followed by impaired smooth-muscle contractility. Changes in excitation threshold, hypertrophic remodeling, and electrical diffusivity produced substantially smaller effects. Pairwise interactions were small relative to the dominant main effects, indicating that the mechanisms contributed largely through their individual effects. Our findings suggest that limiting wall stiffening while preserving smooth-muscle contractile function may provide a therapeutic strategy for maintaining intestinal motility in fibrostenosing Crohn's disease.

bioengineering↗