Advanced-stage ovarian cancer becomes extremely challenging to treat effectively using current surgical and chemotherapy methods due to factors such as peritoneal metastasis, incomplete resection, and drug resistance. While photoimmunotherapy is emerging as a promising option for unresectable metastases, its full potential often goes unrealized due to varying treatment outcomes. This research effort aims to enhance the reliability, safety, and effectiveness of photoimmunotherapy for peritoneal metastases by combining targeted nanotechnology, fluorescence-guided intervention, and a state-of-the-art medical laser system.
Peritoneal metastasis, incomplete resection, and drug resistance render advanced-stage ovarian cancer virtually incurable with current surgical and chemotherapy approaches. Photoimmunotherapy is increasingly used to treat unresectable metastases, but many innovations are lost in translation due to heterogeneous treatment effects. This study integrates targeted nanotechnology, fluorescence-guided intervention, and a medical laser system to improve the safety, efficacy, and consistency of photoimmunotherapy for peritoneal metastases.
This conference presentation was prepared for the Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI conference at SPIE BiOS, SPIE Photonics West 2023.
Photoimmunotherapy employs antibody-photosensitizer constructs (photoimmunoconjugates) for targeted cancer ablation through the generation of reactive oxygen species. While this approach enhances cancer cell specificity, it sacrifices cellular uptake. This study addresses this limitation through two strategies with an emphasis on anti-cancer immunogenicity: 1) utilizing fluid shear stress to mediate delivery, and 2) leveraging nanoengineering approaches to maximize photoimmunoconjugate payload. Results reveal that fluid shear stress promotes photosensitizer delivery and anti-tumor immune response while modulating subcellular localization. By shedding light on improved delivery strategies and formulations, this study generates important implications for the clinical implementation of photoimmunotherapy.
Rationally designed bioconjugates of photosensitizers have been shown to enhance the photochemical effect of photodynamic therapy (PDT) via altering the sub-cellular localization of the photosensitizers or modulating the function of ATP-binding cassette (ABC) transporters. P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are the two key members that contribute to chemoresistance and PDT resistance in cancer. Here, we introduce a porphyrin-based phospholipid conjugation strategy to circumvent and inhibit the efflux function of ABC drug transporters. Our results show the porphyrin-phospholipid conjugate enhances the photosensitizer accumulation and modulates the enzymatic activity and protein integrity of ABCB1 and ABCG2.
Combination treatments are most effective when targeting different cancer survival and growth pathways. Nanotechnology combined with photochemistry provides a unique opportunity to simultaneously deliver and activate multiple drugs that target all major regions of a cancer cell—plasma membrane, cytoplasm, and nucleus. In this study, we developed a light-activatable nanocomplex that selectively and simultaneously deliver three clinically relevant therapeutic agents at a synergistic drug ratio to destroy ovarian cancer cells, while sparing normal tissues.
Over the past few decades, considerable attention has been given to improving the photoactivity and biocompatibility of hydrophobic photosensitizing drugs for light-activatable biomedical applications. It is increasingly clear that photosensitizing biomolecules, based on chemical conjugation or association of photosensitizers with biomolecules (e.g., lipids, polymers, antibodies, and Pluronic), strongly influence the performance of a given photosensitizer in biological environments. However, the numerous studies that have revealed PSBMs are not readily comparable as they cover a wide range of macromolecules, evaluated across a range of experimental conditions. Here, we prepared and characterized a series of well-defined PSBMs and pure drug crystal based on a clinically used photosensitizer—benzoporphyrin derivative (BPD). Our results illuminate the variable trafficking and end effects of clinically relevant PSBMs and BPD nanocrystals, providing valuable insights into methods of PSMB evaluation as well as strategies to select PSMBs based on subcellular targets and cytotoxic mechanisms. More importantly, these results demonstrate that biologically-informed combinations of PSBMs and carrier-free photosensitizers to target multiple subcellular organelles may lead to enhanced therapeutic effects in gliomas.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.