Targeted breast cancer nanotherapeutics: options and opportunities with estrogen receptors

Breast cancer is a multifarious and heterogeneous disease. Identification of molecular alterations of surface/intracellular proteins particularly involved in proliferation and growth of breast cancer cells provides opportunities for the development of new targets for therapy. Several ligands that are routinely employed in targeted delivery to breast cancer cells have been found to be immunogenic. Therefore, endogenous bioligands may serve as a better option, which may be bio-competent and non-immunogenic, including estrogens. Membrane-associated estrogen binding sites are highly over-expressed in cancers of endocrine origin, such as breast. The selective high density of these receptor portals can be utilized for targeted breast cancer therapy. Numerous estrogen-chemotherapeutic agent conjugates have been successfully utilized for targeted drug/DNA delivery. Recently, nanocarrier(s) anchored with estrogens as site-directing ligands for the delivery of bioactive(s) have been exhaustively investigated for breast cancer therapy. This review presents a detail account of how estrogens, anti-estrogens, and their derivatives can be used for site-specific delivery of bioactive(s) to breast cancer cells. The sequential emergence of various estrogen-anticancer drug conjugates is highlighted. Additionally, carrier systems that utilize estrogens/anti-estrogens as ligands for purpose-specific site-selective novel drug delivery platforms have been reviewed and revisited in terms of their realistic clinical applications in breast cancer treatment.