Designing the next generation of small molecule cell surface targetting agents

Supramolecular Self-associating Amphiphiles (SSAs) are a class of molecule invented by JH. To date, members from a library of 100 SSAs have been developed collaboratively with MG 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.

It is hypothesised that the spontaneous self-association of the SSA enables 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.

Aims:
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.

Scientific approach:

JH 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)

JE Lab:
* To use molecular level simulation to understand SSA cell surface interactions and membrane permeation events (Aims 1, 2).

MG 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).

TDL Lab:
* Undertake PK/PD studies within an industrial setting. (Aims 2).

Impact areas:
1. Health - better therapeutic agents for the treatment of cancer.
2. Bioeconomy - Commercialisation of SSA technology.
3. People and talent - Support of women and other marginalised groups within STEM - See later sections for detail.