The use of photocatalytic in situ prodrug activation and against cancer has received increasing attention over recent years. However, the application of the currently approved photocatalysts is limited by their poor aqueous solubility, aggregation, photobleaching, off target effects and poor tumour uptake. One approach to overcome these limitations is through the use of a delivery vector for the photoactive species. Recently we have reported a new class of polymer photocatalysts formed by combining small molecular photocatalysts/ with classical polymer chemistry. 1-3 Creating photocatalytic polymer constructs that contain the beneficial properties from both components. We have designed pH responsive classical polymer catalysts that respond to the well reported pH changes between healthy and cancerous tissue. Here, we have used RAFT polymerisation to produce diblock copolymers consisting of PEG114-b-(PAEMA40-s-PPH2BT2). At pH &gt;7 crosslinking of primary amines in the PAEMA block with terephthalaldehyde occurs, resulting in the formation of nanoparticles (NPs). In this particulate form the polymer is photocatalytically inactive as the active centres are imbedded within the core of the particle. These non-active NPs can freely circulate around the body and will accumulate in tumour tissue through the EPR effect. Within the tumour cell environment a pH drop is observed to pH 6.4. This change stimulates the disassembly of the NP, where the polymer once again becomes photocatalytically active. We have used this photocatalytic material for the in situ activation of a cancer prodrug based on fluorouracil (5-FU). Where the prodrug version of 5-FU shows limited toxicity but can be easily activated in the presence of light and the photoactive polymer into the toxic form. We have demonstrated by both In vitro and cellular studies that this approach has the potential to enable targeted prodrug activation for cancer treatment.

Targeted bioorthoganal prodrug activation enabled by pH responsive classical polymer photocatalysts

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.