Projects

Photodynamic therapy (PDT) is a clinically used modality for treatment and imaging of cancer and non-cancer disease. This photochemistry-based approach involves harmless light excitation of a non-cytotoxic agent (i.e. photosensitizer) to generate cytotoxic molecular species that kill cells and induce tissue damage. Additionally, the fluorescence signal generated from the excited photosensitizer can be used for cancer imaging and for guiding tumor resection. We recently introduced the concept of subtumouricidal photodynamic therapy (referred to as Photodynamic Priming, PDP) and demonstrated its ability to simultaneously overcome chemotherapeutic selection pressure and improve drug delivery, thereby reducing metastases and prolonging animal survival with no additional side effects. Investigations into the role of PDP in modulating tumor-associated extracellular matrix, drug efflux, cancer stem cells, and anti-tumor immunogenicity are ongoing to fully exploit this approach as a tool to enhance tumor permeability, overcome treatment resistance, and prevent distant metastases.

Cancer is a constantly evolving disease that relies on microenvironmental, cellular and molecular compartments to resist and adapt to therapeutic insults. Targeting these adaptive mechanisms requires an understanding of the molecular, cellular and microenvironmental factors that prevent drug delivery and allow cancer cells to survive under adverse conditions. We believe that the most effective cancer treatments will involve interactive regimens that target multiple non-overlapping pathways, preferably such that each component reinforces the other to improve outcomes while minimizing systemic toxicities. Driven by this concept of Mutually-Reinforcing Combination Therapy, a core activity of our lab is to develop and translate photodynamic therapy-based combination regimens to overcome treatment resistance mechanisms and increase therapeutic index in cancer patients.

It is increasingly evident that rationally designed combination treatments impacting multiple molecular targets will most likely improve outcomes in patients with advanced cancer. However, the selective delivery of multiple regimens to the right place, at the right time, and in the correct sequence with consideration of mechanistic interaction remains a major challenge in combination treatment. We leverage bioengineering and photochemistry to develop Multicompartment Light-activatable Nanoplatforms that can deliver three regimens in a unique manner—where one treatment primes the target for the second modality, and the subsequent evasion pathways are mitigated by a third agent; all agents are rationally selected and released in an appropriate time and sequence to account for mechanistic interactions and to improve outcomes. The principle and the nanoplatform developed here will be adaptable to treating a broad range of diseases.