Jonathan F. Lovell

Quantitative Fluorescence Imaging of Chemophototherapy Drug Pharmacokinetics Using Laparoscopic SFDI

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 combined with chemotherapeutic like Doxorubicin (Dox) to enable light-triggered drug release and targeted tumor destruction. Here, we present the validation of a wide-field laparoscopic spatial frequency domain imaging (SFDI) system in an ovarian cancer model. The system allows quantitative fluorescence imaging to obtain absolute drug concentrations in vivo to obtain the absolute concentrations of PoP and Dox fluorescence by correcting for tissue absorption and scattering effects. Fluorescence imaging revealed a significant reduction (~25%, p < 0.001) in PoP concentration in tumor regions post-illumination, demonstrating PDT-mediated photobleaching. Next, the Dox release experiment showed an increase of ~13 µg/mL Dox concentration at the local site. The ability to quantify both PoP and Dox fluorescence concentrations with a laparoscopic system underscores its potential for intraoperative monitoring of CPT efficacy. These findings indicate wide-field laparoscopic SFDI as a promising tool for guiding minimally invasive PDT and targeted drug delivery in preclinical and future clinical settings.

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 for the effects of tissue optical properties but also ensures accurate drug delivery to deep-seated tumors. Preliminary results validate the probe’s 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 that involve optimizing chemotherapy administration for precision and control.

Chemophototherapeutic Ablation of Doxorubicin‐Resistant Human Ovarian Tumor Cells†

AbstractPorphyrin‐phospholipid (PoP) liposomes loaded with Doxorubicin (Dox) have been demonstrated to be an efficient vehicle for chemophototherapy (CPT). Multidrug resistance (MDR) of cancer cells is a problematic phenomenon in which tumor cells develop resistance to chemotherapy. Herein, we report that Dox‐resistant tumor cells can be ablated using our previously described formulation termed long‐circulating Dox loaded in PoP liposomes (LC‐Dox‐PoP), which is a PEGylated formulation containing 2 mol. % of the PoP photosensitizer. In vitro studies using free Dox and LC‐Dox‐PoP showed that human ovarian carcinoma A2780 cells were more susceptible to Dox compared to the corresponding Dox‐resistant A2780‐R cells. When CPT was applied with LC‐Dox‐PoP liposomes, effective killing of both nonresistant and resistant A2780 cell lines was observed. An in vivo study to assess the efficiency of LC‐Dox‐PoP showed effective tumor shrinkage and prolonged survival of athymic nude mice bearing subcutaneous Dox‐resistant A2780‐R tumor xenografts when they were irradiated with a red laser. Biodistribution analysis demonstrated enhanced tumoral drug uptake in Dox‐resistant tumors with CPT, suggesting that increased drug delivery was sufficient to induce ablation of resistant tumor cells.