Drug-Loaded Nanomicelles Conjugated To Mucin Antibodies For Direct Targeting Of Ovarian Cancer Cells Expressing Mucin Antigens – Prof Viness Pillay
Prof Viness Pillay
- Wits Medical School, Department of Pharmacy and Pharmacology, University of the Witwatersrand
Drug-Loaded Nanomicelles Conjugated To Mucin Antibodies For Direct Targeting Of Ovarian Cancer Cells Expressing Mucin Antigens.
Ovarian cancer (OC) is a challenging disease to treat and since it presents with few early symptoms, it is usually diagnosed late when in advanced stages. This study innovatively focuses on the combinatorial use of mucins such as MUC1, MUC4 and MUC16 for the design and development of a novel OC cell-targeting intraperitoneal drug delivery system to drastically improve the current chemotherapy of OC. The proposed mechanism of innovation is by employing antibody-conjugated nanomicelles to target mucin antigens expressed on OC cells. To our knowledge this has not been explored before. Ovarian tumors exhibit diverse and altered cell surface antigens such as, HE4, CA72-4, EGFR, SMRP and mucin (MUC16) that discriminate them from normal ovary cells and other normal cells lining the peritoneum. MUC16 is a known cell surface antigen in OC and since it is shed into the serum, it is widely used for diagnosing and managing epithelial OC. Mucins are synthesized in epithelial cells within the human body and protect epithelial cells from infection and injury by maintaining their hydrated and lubricated surfaces. During malignant transformation, the glycosylation of the mucin peptide backbone is altered, resulting in novel carbohydrate epitopes or the exposure of the peptide backbone. This change in mucin expression results in the loss of polarity of the epithelial cells and the subsequent increase in synthesis results in large quantities of mucin being either shed or secreted by tumor cells for metastasis and adhesion forming secondary tumor nodules. MUC16, a serum marker for OC, has been shown to facilitate the immune escape of OC cells. The non-specific distribution of chemotherapeutic drugs to tissues other than the tumor is one of the major undesirable side-effects of chemotherapy and this study therefore attempts to overcome this limitation by using MUC16 antibody-conjugated antineoplastic drug-loaded nanomicelles to target OC cells.
This research relates to the CANSA defined sphere of “Early diagnosis of Cancer” and “Prevention of Cancer”. It also touches on population health geared towards providing a new medical product that will ultimately lead to actual and measurable improvements in the treatment of ovarian cancer of the population which is currently sub-optimally treated and exacerbates the burden of disease.
Merging the research areas of Gynecological Oncology, Nanotechnology and Pharmaceutical Sciences for the design of the antibody-conjugated antineoplastic drug-loaded nanomicelles to target ovarian cancer cells constitutes the following specialist area of research:
- Oncology (treatment of ovarian cancer to ensure optimal health)
- Pharmaceutics (design of a biodegradable nano-enabled device as an intraperitoneal implant for site-specific delivery of antineoplastic drugs in treating ovarian cancer