The Day Lab has extensive experience developing and implementing nanoparticles as tools for photoresponsive therapy. Some of these treatments are described below:
Photothermal therapy (PTT) is a treatment in which plasmonic nanoparticles or nanoparticles containing light-reactive dyes are delivered to tumors either intravenously or intratumorally. Subsequent exposure of the tumor to near-infrared (NIR) light, which is minimally absorbed by normal tissue components, causes the nanoparticles to produce heat that irreversibly damages the cancer cells leading to tumor regression. This approach to cancer treatment is advantageous because therapeutic effects are achieved only where light and nanoparticles are combined at the tumor site, mitigating off-target side effects.
In collaboration with Dr. Joel Rosenthal’s lab in the Department of Chemistry and Biochemistry at the University of Delaware, we have also developed strategies for photodynamic cancer therapy (PDT). In PDT, photosensitizes that are excited with light transfer the absorbed energy to adjacent tissue oxygen molecules to produce toxic singlet oxygen that damages cancer cells. We have shown that combining PDT with PTT is synergistic, and are currently working to create new photosensitizer-nanoparticle conjugates with enhanced photophysical properties.
Light-Triggered Payload Release
Off-target toxicity is a major limitation in drug and RNA delivery, so we are creating photoresponsive nanoparticles to enable light-triggered release of payloads in diseased tissues. For example, we have shown that nanoshells can enable light-triggered release of RNA molecules that are tethered to their surface to elicit on-demand gene regulation. This strategy offers unprecedented control over the site and timing of payload delivery.
1. Wang J*, Potocny AM*, Rosenthal J#, Day ES#. Gold nanoshell-linear tetrapyrrole conjugates for near infrared-activated dual photodynamic and photothermal therapies. ACS Omega. 2019; http://dx.doi.org/10.1021/acsomega.9b04150. *co-first authors #co-corresponding authors
2. Valcourt DM, Dang MN, Day ES. IR820-loaded PLGA nanoparticles for photothermal therapy of triple-negative breast cancer. Journal of Biomedical Materials Research Part A. 2019; 107A: 1702-1712.
3. Riley RS*, O’Sullivan RK*, Potocny AM, Rosenthal J#, Day ES#. Evaluating nanoshells and a potent biladiene photosensitizer for dual photothermal and photodynamic therapy of triple negative breast cancer cells. Nanomaterials. 2018; 8, 658. *co-first authors #co-corresponding authors
4. Potocny AM*, Riley RS*, O’Sullivan RK, Day ES#, Rosenthal J#. Photochemotherapeutic properties of a linear tetrapyrrole palladium(II) complex displaying an exceptionally high phototoxicity index. Inorganic Chemistry.2018; 57(17): 10608-10615. *co-first authors #co-corresponding authors
5. Riley RS, Day ES. Gold nanoparticle-mediated photothermal therapy: applications and opportunities for multimodal cancer treatment. WIRES Nanomedicine & Nanobiotechnology. 2017; e1449.
6. Riley RS, Dang MN, Billingsley MM, Abraham B, Gundlach L, Day ES. Evaluating the mechanisms of light-triggered siRNA release from nanoshells for temporal control over gene regulation. Nano Letters. 2018; 18(6): 3565-3570.
7. Fay BL, Melamed JR, Day ES. Nanoshell-mediated photothermal therapy can enhance chemotherapy in inflammatory breast cancer cells. International Journal of Nanomedicine. 2015; 10: 6931-6941.
8. Melamed JR*, Edelstein RS*, Day ES. Elucidating the fundamental mechanisms of cell death triggered by photothermal therapy. ACS Nano. 2015; 9(1): 6-11. *co-first authors.