Biology subjects

Sunar, U.

Publications and source records attributed to Sunar, U..

8 recordsLinked to original sources

bioRxiv2026

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

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.

bioengineering↗

bioRxiv2026

Depth-Sensitive Optical Property Characterization Using Multi-Frequency Laparoscopic SFDI

Accurate knowledge of tissue absorption (a) and reduced scattering [Formula] parameters are required to plan and monitor laparoscopic chemophototherapy (CPT) in ovarian cancer, including light dosimetry and quantitative fluorescence mapping of porphyrin-phospholipid (PoP) photobleaching and light-triggered doxorubicin (Dox) release. We implemented a depth-sensitive, multi-frequency laparoscopic spatial frequency domain imaging (SFDI) framework to improve optical-property estimation in layered tissue. A DMD-based laparoscope imaged two-layer phantoms with controlled optical contrasts and superficial thicknesses. Spatial-frequency subsets associated with different penetration depths were independently fit to recover a and [Formula], and compared with a two-layer diffusion model. Recovered [Formula] values remained bounded by the known layer references and shifted monotonically toward the superficial value as spatial frequency and top-layer thickness increased, approaching a single-layer response at high frequency/thick layers. Quantitative model comparison showed {delta}-P1 variants outperformed the standard diffusion approximation, reducing RMSPE between modeled and measured [Formula] to 0.8-6.5% (silicone/silicone) and 1.6-8.3% (silicone/intralipid), whereas SDA errors reached [~]13.8% and 21.1%, respectively. This approach demonstrates multi-frequency laparoscopic SFDI as a practical initial step for depth-sensitive fluorescence correction for individualized CPT treatment planning and monitoring.

bioengineering↗

bioRxiv2025

Depth-Sensitive Assessment of Cerebral Blood Flow and Low-Frequency Oscillations After Traumatic Brain Injury in Mice Using Time-Gated Diffuse Correlation Spectroscopy

Traumatic brain injury (TBI) can lead to long-lasting impairments in cerebral perfusion, making early detection of microvascular changes critical for guiding clinical interventions. In this study, we employed time-gated diffuse correlation spectroscopy (TG-DCS) at 1064 nm to non-invasively quantify depth-resolved cerebral blood flow (CBF) and low-frequency oscillations (LFOs) in a mouse model of closed-head injury. By analyzing early (superficial) and late (deeper) photon arrival times, we identified a significant drop in CBF shortly after injury, with a partial recovery observed at 2 hours post-trauma. Power spectral analysis of the blood flow index revealed significant alterations in LFO bands, particularly in slow-5 (0.01-0.027 Hz) and slow-3 (0.073-0.198 Hz) ranges, with p < 0.05 at both early and late gates. These changes were more pronounced than BFI alterations alone, indicating that LFOs may serve as sensitive biomarkers of neurovascular disruption. Our findings demonstrate the feasibility of TG-DCS for depth-specific monitoring of cerebral hemodynamics and oscillatory dynamics after TBI and suggest its potential utility in translational neurotrauma research.

bioengineering↗

bioRxiv2025

Quantitative Fluorescence Imaging of Porphyrin Phospholipid Photobleaching and Light Activated Liposomal Doxorubicin Release Using Wide-field and Laparoscopic SFDI in an Ovarian Cancer Model

Chemophototherapy (CPT) is an emerging cancer treatment that leverages the synergistic effects of photodynamic therapy (PDT) and chemotherapy. This approach utilizes photosensitizers like Porphyrin Phospholipid (PoP) and Doxorubicin (Dox) to enable phototriggered drug release and targeted tumor destruction. In this study, we present the development and validation of a wide-field laparoscopic spatial frequency domain imaging (SFDI) system, designed to improve intraoperative quantitative fluorescence imaging and monitoring of PoP photobleaching, a PDT-driven effect for tumor destruction, and light-activated Dox release, which facilitates targeted chemotherapeutic drug delivery in an ovarian cancer model. Compared to previous flexible endoscopic imaging methods, our laparoscopic SFDI system offers enhanced spatial coverage, enabling accurate wide-field optical property quantification in minimally invasive surgical settings. Using this system, we performed quantitative fluorescence imaging in vivo to obtain absolute concentrations of PoP and Dox fluorescence, correcting for tissue absorption and scattering effects. This capability allows for precise assessment of PoP photobleaching and Dox release kinetics with improved spatial resolution. Fluorescence imaging revealed a significant reduction in PoP concentration in tumor regions post-illumination, demonstrating the PDT-mediated photobleaching effect and successful light-triggered drug release activation for chemo-induced tumor destruction. The ability to differentiate PoP and Dox fluorescence in a laparoscopic system underscores its potential for real-time intraoperative monitoring of CPT efficacy. These findings establish wide-field laparoscopic SFDI as a promising tool for guiding minimally invasive photodynamic therapy and targeted drug delivery in clinical settings.

bioengineering↗

bioRxiv2024

Fluence rate-dependent kinetics of light-triggered liposomal doxorubicin assessed by quantitative fluorescence-based endoscopic probe

Liposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin-phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery. By integrating diffuse reflectance and fluorescence spectroscopy, our approach not only corrects the effects of tissue optical properties but also ensures accurate drug delivery to deep-seated tumors. Pre-liminary results validate the probe effectiveness in controlled settings, highlighting its potential for future clinical adaptation. This study sets the stage for in vivo applications, enabling the exploration of next-generation treatment paradigms for the management of cancer by optimizing chemotherapy administration with precision and control.

bioengineering↗

bioRxiv2022

Chemophototherapy Overcomes Doxorubicin Resistance in Human Ovarian Cancer Cells

Porphyrin-phospholipid (PoP) liposomes loaded with Doxorubicin have been demonstrated to be an efficient vehicle for chemophototherapy (CPT). Multi-drug resistance (MDR) of cancer cells is a known resistance mechanism for cancer chemotherapies. We report a phototherapeutic measure to overcome Dox-resistance using Doxorubicin (Dox)-loaded PoP liposomes. In vitro studies using free Dox or Dox loaded into liposomes with 2 mol.% showed human ovarian carcinoma A2780 cells were more susceptible to these drugs compared to the corresponding Dox-resistant A2780-R cells. In contrast, when CPT was applied with LC-Dox-PoP liposomes, effective killing of both non-resistant and resistant A2780 cell lines was observed. An in vivo study to assess the efficiency of LC-Dox-PoP liposomes with phototreatment showed effective tumor shrinkage and prolonged survival of athymic nude mice bearing A2780-R tumor xenografts. Biodistribution analysis demonstrated enhanced tumoral drug uptake in Dox-resistant tumors with CPT, pointing to the likelihood that increased drug delivery overcame resistance mechanisms to provide for improved anti-cancer therapy.

bioengineering↗

bioRxiv2020

Quantification of Hypoperfusion in Autism Assessed by Diffuse Correlation Spectroscopy and Frequency Domain Near Infrared Spectroscopy

There is a need for quantitative biomarkers for early diagnosis of autism. We showed previously that hemoglobin concentrations show contrast between autistic group vs control group in humans. Cerebral blood flow can provide additional sensitivity for improved characterization. Diffuse correlation spectroscopy (DCS) has been shown to be reliable method to obtain blood flow contrast in animals and humans. Thus, in this study we evaluated DCS in an established autism model. Our results indicate that autistic group had significantly lower blood flow compared to control group. These results confirm the previous results obtained from humans by positron emission tomography and magnetic resonance imaging.

bioengineering↗

bioRxiv2020

Deep learning model for ultrafast quantification of blood flow in diffuse correlation spectroscopy

Diffuse correlation spectroscopy (DCS) is increasingly used in the optical imaging field to assess blood flow in humans due to its non-invasive, real-time characteristics and its ability to provide label-free, bedside monitoring of blood flow changes. Previous DCS studies have utilized a traditional curve fitting of the analytical or Monte Carlo models to extract the blood flow changes, which are computationally demanding and less accurate when the signal to noise ratio decreases. Here, we present a deep learning model that eliminates this bottleneck by solving the inverse problem more than 2300% faster, with equivalent or improved accuracy compared to the nonlinear fitting with an analytical method. The proposed deep learning inverse model will enable real-time and accurate tissue blood flow quantification with the DCS technique.

bioengineering↗