Abstract
Cervical cancer accounts for 500,000 new cases and 250,000 deaths in women worldwide. In low-income countries, cervical cancer is the most common cause of cancer-related deaths among women. Novel approaches for the early detection and aggressive treatment of cervical cancer are urgently needed to increase the survival rates. To this end, a promising strategy that might improve the specificity of current diagnostic and therapeutic agents is the development of drugs or contrast agents targeting glycans, polysaccarides decorating normal and cancerous cells that provide a unique fingerprint on the cell surface. Tumor glycans are important in regulating pivotal events during the development and progression of cancer. Changes in their sequence and structure are known to be responsible for cell proliferation, invasion, angiogenesis, and metastasis. Malignant transformation of cervical cells is accompanied by the expression of specific glycans that are absent on normal uterine cervix cells. Peptide-based ligands specific for these cervical cancer glycans have been discovered, and their use as tumor-homing agents for diagnostics and therapeutic purposes has been explored in xenograph models. We have currently developed an innovative drug delivery vehicle for the simultaneous and highly specific imaging and treatment of cervical cancer. To take full advantage of the enhanced permeability and retention effect (EPR) of the nanocarriers and to have deep penetration inside the tumor mass, we have developed a telodendrimer system, comprised of clusters of oligomeric cholic acids (CA) linked to a polyethylene glycol (PEG) chain which self-assemble within an aqueous environment with tunable sizes and efficient drug loading capacity. This vehicle consists of a nanocarrier loaded with the powerful anticancer drug, doxorubicin, and decorated with cervical cancer specific ligands targeting cell surface glycans. Thanks to the presence of the targeting ligands, the nanocarriers carry the otherwise non-selective drug specifically into the targeted cancer cells leading to release of anticancer drug only where needed. Because of the lower doses and the relatively low cost of the nanoparticle employed as drug carriers, we envision that this technology will be amendable for clinical translation and will be a powerful therapeutic tool to address the needs and disparities typical of less developed countries.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A49.