Developing cellular micromotors to improve ovarian cancer management

Abstract

High grade serous ovarian cancer is the most lethal gynaecological malignancy in the developed world. Due to a lack of symptoms and a lack of reliable early detection methods, it is often diagnosed at a late stage after it has already metastasised. Therefore, new tools for diagnosis and treatment are urgently required. Over recent years, it has been established that serous tubal intraepithelial carcinoma lesions arise in the fallopian tubes as precursors to high grade serous ovarian cancer. There is an approximately seven-year window between the appearance of these lesions and their development into ovarian cancer, which represents an opportunity for early detection and treatment. Sperm cells are uniquely placed to fill this niche as they are perfectly adapted to swim up into the fallopian tubes, which are difficult to reach via conventional, non-invasive methods. This report details progress towards the development of theranostic "spermbots" engineered to detect and eradicate lesions in the fallopian tube before they spread to the ovaries. This includes loading of sperm cells with a fluorescent analogue of the ovarian cancer drug olaparib, co-loading sperm with olaparib and the chemotherapeutic drug Dox-HCl, decorating the surface of sperm cells with cell surface marker-targeting antibodies, and progress towards combining drug loading and targeting approaches. Additionally, a proteomics screen identified several potential biomarkers for ovarian cancer precursors in patient samples. Significant progress has been made towards the engineering of sperm as theranostic drug-delivery vehicles, and future experiments will focus on establishing the effects of these "spermbots" in vivo.

Date of Award	1 Aug 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Christine Schmidt (Supervisor), Stephen Taylor (Supervisor), Daniel Brison (Supervisor) & Richard Edmondson (Supervisor)