Stras, Sally. Environmentally responsive liposomes for treatment of metastatic triple negative breast cancer. Retrieved from https://doi.org/doi:10.7282/T3R78JNH
DescriptionIn 2015, it was estimated that approximately 1.7 million women were diagnosed with breast cancer in the United States alone. Breast cancer is the most common cancer among women. One in eight women in their lifetime will have to endure the tribulations of discovering that they have breast cancer and all that comes in hopes of beating the disease. Triple-negative breast cancer (TNBC) is a subgroup of breast cancer associated with a poor prognosis and a higher chance of cancer metastasis outside the breast. TNBC is defined as being negative in gene expression for estrogen receptor (ER), progesterone receptor (PR) and lacking gene expression of HER2/neu. Current methods for targeting TNBC tumors remain in investigative stages due to the difficulty in discovering an appropriate and direct method of targeting. To enable selective and effective treatment of TNBC solid tumors, we study a drug delivery carrier of cisplatin (CDDP) - a clinically accepted major line of therapy for TNBC - that is designed to ultimately result in (a) deep penetration and homogeneous distribution of the drug within tumors and (b) enhanced ii uptake by the cancer cells that constitute these tumors. Towards these aims, we engineered a carrier that is a tunable (pH-sensitive) liposome encapsulating cisplatin. These liposomes are designed to form lipid-phase separated domains at acidic pH. Domain formation is tuned to trigger content release, and the change is pH is used to increase the adsorptive/adhesive property of these liposomes. Improved tumor penetration of delivered cisplatin is expected to be achieved by triggered release of cisplatin directly within the tumor interstitial region from extravasated liposomes. Further increase in intracellularly delivered cisplatin (due to more favorable retention of liposomes by solid tumors in vivo) is expected to be achieved by liposomes that are functionalized with an adhesive switch on their surface with the aim to slow their clearance from the tumor.