Novel Tamoxifen Nanoformulations for Improving Breast Cancer Treatment: Old Wine in New Bottles

Abstract

Breast cancer (BC) is one of the leading causes of death from cancer in women; second only to lung cancer. Tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA for hormone therapy of BC. Despite having striking efficacy in BC therapy, concerns regarding the dose-dependent carcinogenicity of TAM still persist, restricting its therapeutic applications. Nanotechnology has emerged as one of the most important strategies to solve the issue of TAM toxicity, owing to the ability of nano-enabled-formulations to deliver smaller concentrations of TAM to cancer cells, over a longer period of time. Various TAM-containing-nanosystems have been successfully fabricated to selectively deliver TAM to specific molecular targets found on tumour membranes, reducing unwanted toxic effects. This review begins with an outline of breast cancer, the current treatment options and a history of how TAM has been used as a combatant of BC. A detailed discussion of various nanoformulation strategies used to deliver lower doses of TAM selectively to breast tumours will then follow. Finally, a commentary on future perspectives of TAM being employed as a targeting vector, to guide the delivery of other therapeutic and diagnostic agents selectively to breast tumours will be presented.

Concept Design, Development and Preliminary Physical and Chemical Characterization of Tamoxifen-Guided-Mesoporous Silica Nanoparticles

“…The use of selective estrogen receptor modulators (SERMs) to block the effects of endogenous estrogen in breast tissues by competing with estrogen for ER binding has been established as one of the most effective strategies in BC therapy [ 24 , 25 ]. The treatment of BC with tamoxifen (TAM) has been the gold standard of hormonal therapy since 1973 and has been used as an affordable, life-saving tool for millions of women worldwide [ 26 ]. We recently reviewed how low concentrations of TAM can be employed as a targeting vector to direct the delivery of nanosystems containing other anticancer agents to solid tumours [ 26 ].…”

“…The treatment of BC with tamoxifen (TAM) has been the gold standard of hormonal therapy since 1973 and has been used as an affordable, life-saving tool for millions of women worldwide [ 26 ]. We recently reviewed how low concentrations of TAM can be employed as a targeting vector to direct the delivery of nanosystems containing other anticancer agents to solid tumours [ 26 ]. For example, Jain and colleagues incorporated TAM molecules into the lipid bilayers of liposomes, to guide the delivery of doxorubicin to ER+ tumours, which resulted in an improved uptake of liposomal doxorubicin by tumours, and subsequently higher rates of tumour cell death [ 27 ].…”

Combination Therapy and Nanoparticulate Systems: Smart Approaches for the Effective Treatment of Breast Cancer

“…The best-suited therapy for HR-positive BC is by targeting the estrogen receptors, and these hormone levels can either be reduced or blocked. The estrogen receptor (ER) blockers, such as tamoxifen, prevent the attachment of estrogen, arresting the BC growth [ 7 ]. Fulvestrant is another drug that belongs to the class of estrogen-degrading agents, which selectively destroy the estrogen receptors [ 8 ].…”

Tamoxifen and the PI3K Inhibitor: LY294002 Synergistically Induce Apoptosis and Cell Cycle Arrest in Breast Cancer MCF-7 Cells

“…Tamoxifen (TAM) is the oldest and most-prescribed selective estrogen receptor modulator, that has been approved to treat women and men diagnosed with hormonal receptor (HR + ), early-stage BC after surgery to reduce the risk of the cancer recurrence as well as treatment of advanced-stage or metastatic HR + BC patients [ 7 , 8 , 9 ]. The combination of high efficacy in both pre- and postmenopausal women and a good tolerability profile of TAM lead to maintain its position as drug of choice for most patients with HR + breast cancer [ 7 ].…”