Glioblastoma stem cells (GSCs) isolated from patients with newly diagnosed disease are potent tumor initiators that express biomarkers associated with stem cells. These stem-like cells are thought to drive treatment resistance and tumor recurrence. Preclinical models suggest that the GSC subpopulation becomes enriched and re-populates the tumor milieu following conventional therapies. This talk will discuss the use of photodynamic therapy to overcome treatment resistance in a preclinical model of human GSC neurosphere cell cultures.
Lack of access to effective cancer therapeutics in resource-limited settings is widely implicated in global cancer health disparities. Here we evaluate low-cost devices to enable photodynamic therapy (PDT) and associated photosensitizer imaging in regions with little or no access to electricity or medical infrastructure. We demonstrate the efficacy of a battery-powered LED-based device following aminolevulinic acid (ALA) induced accumulation of protoporphyrin IX (PpIX). We further evaluate the capability of a consumer smartphone coupled with a 405nm LED array and a PpIX emission filter to image PpIX fluorescence. Collectively this work suggests the feasibility of image-guided ALA-PDT in resource-limited settings.
Photodynamic therapy (PDT) is a photochemistry-based modality in which a chemical (photosensitizer) is energized by light to produce cytotoxic molecular species. The current state of the art limits PDT to small isolated lesions. To make the modality more broadly applicable, new targeting strategies with high payloads of the photosensitizer are needed and several approaches are being evaluated. Nanoliposomes have attracted interest as efficient, biocompatible and biodegradable carriers of photosensitizers that broaden the applications of PDT through their multi-compartmental architecture and their tunable physicochemical characteristics. This chapter provides an overview of the theranostic aspects of liposomal constructs and their role in future advancements of PDT. It also elaborates on the photochemistry, physical properties and release mechanisms of photosensitizers entrapped within optimized liposomes that mediate effective PDT treatments.
Assessment of molecular signatures of tumors in addition to their anatomy and morphology is desired for effective diagnostic and therapeutic procedures. Development of in vivo imaging techniques that can identify and monitor molecular composition of tumors remains an important challenge in pre-clinical research and medical practice. Here we present a molecular photoacoustic imaging technique that can visualize the presence and activity of an important cancer biomarker – epidermal growth factor receptor (EGFR), utilizing the effect of plasmon resonance coupling between molecular targeted gold nanoparticles. Specifically, spectral analysis of photoacoustic images revealed profound changes in the optical absorption of systemically delivered EGFR-targeted gold nanospheres due to their molecular interactions with tumor cells overexpressing EGFR. In contrast, no changes in optical properties and, therefore, photoacoustic signal, were observed after systemic delivery of non-targeted gold nanoparticles to the tumors. The results indicate that multi-wavelength photoacoustic imaging augmented with molecularly targeted gold nanoparticles has the ability to monitor molecular specific interactions between nanoparticles and cell-surface receptors, allowing visualization of the presence and functional activity of tumor cells. Furthermore, the approach can be used for other cancer cell-surface receptors such as human epidermal growth factor receptor 2 (HER2). Therefore, ultrasound-guided molecular photoacoustic imaging can potentially aid in tumor diagnosis, selection of customized patient-specific treatment, and monitor the therapeutic progression and outcome in vivo.
Selection and design of individualized treatments remains a key goal in cancer therapeutics; prediction of response and tumor recurrence following a given therapy provides a basis for subsequent personalized treatment design. We demonstrate an approach towards this goal with the example of photodynamic therapy (PDT) as the treatment modality and photoacoustic imaging (PAI) as a non-invasive, response and disease recurrence monitor in a murine model of glioblastoma (GBM). PDT is a photochemistry-based, clinically-used technique that consumes oxygen to generate cytotoxic species, thus causing changes in blood oxygen saturation (StO2). We hypothesize that this change in StO2 can be a surrogate marker for predicting treatment efficacy and tumor recurrence. PAI is a technique that can provide a 3D atlas of tumor StO2 by measuring oxygenated and deoxygenated hemoglobin. We demonstrate that tumors responding to PDT undergo approximately 85% change in StO2 by 24-hrs post-therapy while there is no significant change in StO2 values in the non-responding group. Furthermore, the 3D tumor StO2 maps predicted whether a tumor was likely to regrow at a later time point post-therapy. Information on the likelihood of tumor regrowth that normally would have been available only upon actual regrowth (10-30 days post treatment) in a xenograft tumor model, was available within 24-hrs of treatment using PAI, thus making early intervention a possibility. Given the advances and push towards availability of PAI in the clinical settings, the results of this study encourage applicability of PAI as an important step to guide and monitor therapies (e.g. PDT, radiation, anti-angiogenic) involving a change in StO2.