Project No. 2228
Dr Jennifer Hiscock – University of Kent
Prof Michelle Garrett – University of Kent
Prof Jonathan Essex – University of Southampton
Dr Hamish Ryder – CRUK Therapeutic Discovery Laboratories
Supramolecular Self-associating Amphiphiles (SSAs): a novel class of cell membrane active therapeutic agents?
To date, members from a library of ≈ 100 SSAs have been developed as both ovarian/glioblastoma anticancer agents and efficacy enhancers for a range of currently used therapies to which there is known resistance, such as cisplatin.
SSAs are known to self-associate to from vesicle-like structures that we hypothesise to enable the effective delivery of this agent and/or a molecular cargo to the surface of the cell. These SSAs then selectively interact with and permeate a target cancer cell membrane resulting in a therapeutic effect and/or the delivery of a molecular cargo to the inside of the cell.
1. Determine bulk membrane self-association and permeation processes for
current lead anticancer SSAs.
2. Characterise the anticancer activity of these SSAs against resistant/non-
resistant ovarian cancer cell lines and determine the suitability of these
agents for use in the clinic.
3. Use project outputs to inform design of next generation SSAs.
Jennifer Hiscock Lab:
* Synthesis and design of novel SSAs (Aims 1, 3).
* To perform patch clamp, membrane fluidity and vesicle leakage
experiments to ascertain SSA interaction with model cell membranes.
(Aims 1, 3)
Jonathan Essex Lab:
* To use molecular level simulation to understand SSA cell surface interactions and membrane permeation events (Aims 1, 2).
Michelle Garrett Lab:
* Determine cellular cytotoxicity of SSAs on ovarian cancer
cells versus normal cells (Aims 2, 3).
* Undertake microscopy studies to understand membrane permeation
processes (Aim 2).
Therapeutic Discovery Laboratories (Hamish Ryder) Lab:
* Undertake PK/PD studies within an industrial setting. (Aim 2).
1. Health – better therapeutic agents for the treatment of cancer.
2. Bioeconomy – Bringing SSA technology from the lab bench into the clinic.