Evolution as well as the mechanism of Photodynamic Therapy and Priming (PDT/P). PDP can be leveraged to permeabilize the tumor vasculature, overcome biological barriers, modulate multidrug resistance, enhance immune responses, increase tumor permeability and enable the photochemical release of drugs for the treatment of cancer. (Obaid et al., Nat Rev Bioeng., 2024)Macromolecular targeted PDT is typically done by using targeting moieties that are directed to tumor cells, tumor neovasculature, tumor-associated cells (e.g.cancer associatedfibroblasts, tumor associated macrophages etc.), or various combinations of these. The above graphic highlights the five main molecular targeted PDT modalities: full-length antibodies, engineered proteins, natural ligands, immune checkpoint inhibitors, and biomimetic membranes. (Quaye et al., Current Opinion in Chemical Biology)For the first time, we have developed a solid lipid nanoformulation of lipidated benzoporphyrin derivative photosensitizer (LNP BPD-PC) which resembles the composition of the SpikevaxⓇ Moderna COVID-19 vaccine. We have then compared it to an existing liposomal formulation (Lipo BPD-PC) and found that Lipo BPD-PC is able to generate 17% more singlet oxygen than LNP BPD-PC, while, LNP BPD-PC is able to produce 76% more hydroxyl radicals and/or peroxynitrite anion. Interestingly, PDT using LNP BPD-PC was more efficient at inducing immunogenic cell death (calreticulin membrane translocation) than Lipo BPD-PC when using IC25 and IC50 PDT doses. (Shah et al., ACS Applied Bio Materials)For the first time, we show that Cet-IRDye800CW is capable of antibody-targeted PDT in vitro when the payload of dye molecules is increased from 2 (clinical version) to 11 per antibody. This approach could hold potential for eliminating residual disease postoperatively when using sustained illumination devices, such as fiber optic patches and implantable surgical bed balloon applicators. (Nguyen et al., Mol. Pharmaceutics 2024)A single PD-L1 immune checkpoint targeted photoactivable liposome (iTPAL) construct we developed exhibits tumor cell-specific phototoxicity through PD-L1 targeting, blocks the PD-1/PD-L1 immune checkpoint, induces immunogenic cell death, primes tumor collagen to promote self-delivery through solid PDAC tumors, inhibit tumor growth and improve survival even with a single sub-curative dose in mice bearing CT1BA5 pancreatic tumors. (Bhandari et al., Adv. Healthcare Mater., 2024)
Remediating desmoplasia is correlated with improved survival outcomes in mice bearing pancreatic cancer. The relative tumor content of collagen I, II and III was inversely correlated with overall survival while, surprisingly, the relative tumor content of collagen IV was directly correlated with overall survival. (Obaid et al., Journal of Photochemistry and Photobiology, 2023)
Photodynamic Priming induces immunogenic cell death by releasing Damage Associated Molecular Patterns (DAMPs) and improves the bulk delivery of ⍺-PD-L1 antibodies in head and neck tumors. (Bhandari et al., Photochemistry and Photobiology, 2023)
PhD students Chanda and Nimit performing in vivo studies on mice bearing pancreatic tumors. In this study, a novel tumor-targeting light activable drug was administered intravenously in mice, activated using 690 nm light and imaged for its biodistribution using a Pearl Trilogy.
Our students Sid, Micah and Austin very happy at work!
Our undergraduate student Azophi very focused on performing histological studies on tumor tissues!
Our undergrad student Sid hard at work performing longitudinal nanoconstruct stability testing!
Our newest undergraduate student Micah all set to perform a cell viability assay on head and neck cancer cells!
