Tamoxifen (TAM), as a hydrophobic drug, is a selective estrogen modulator (SERM) applied to hormone therapy for breast cancer (BC). Although it is effective and affordable in BC therapy, there are some important challenges in the use of TAM. The major one is the side effects related to conventional doses, and decreasing the dose of TAM is the main solution. By using novel TAM-containing nanoformulations instead of chemotherapy, toxic effects will be greatly decreased. Nanocarriers are able to carry small amounts of TAM to tumors during a long time and limit their dose-dependent toxicity. Many attempts have been made to prepare TAM-loaded nanoformulations from different nanomaterials like liposomes, polymeric NPs, micelles, solid lipid nanoparticles, protein-based NPs, dendrimers, and other types of nanoparticles. Another important problem of TAM nanocarriers is the compatibility of nanoformulations with biological environments. Hence, understanding how different cell types respond to exposure to nanomaterials to assess the risks and advantages of nanomaterials is important. With increasing knowledge in this field, the development of improved formulations to remove the potential toxicity risk of nanomaterials on healthy cells will be available. The poisonous nature of nanoscale compoundscan beameliorated by modifying the surface like PEGylation (PEG). Small amounts of TAM can also be employed in directing the delivery ofnanoformulations containing different cargoes into cancer cells like ER + BC cells as a guiding vector. Stimulus-responsive drug delivery systems design is an emerging field in nanocarriers. In these systems, some features of the drugs can be modullatedin response to external and intrinsic physiochemical factors, like release profiles in a sustained manner and targeted permeation. Novel drug delivery systems could be synthesized by incorporating TAM into these carriers which have great therapeutic potential.
