Breast cancer is one of the most prevalent cancer, with the second rank in the mortality rate of women after lung cancer.1 In 2020, approximately 276,480 new breast cancer cases (30 % of total cases) and 42,170 breast cancer deaths (15 % of the total cancer deaths) were estimated throughout the United states.2 Current therapeutic approaches for breast cancer rely on surgical resection, radiation, and chemotherapeutic agents.3, 4, 5 Doxorubicin (DOX) is widely used in chemotherapy, which possesses high anti-tumor activity. It is clinically used to treat a variety of cancers such as bladder, cervix, leukemia, lung, lymphoma, ovary, prostate, stomach, and breast cancer.6, 7, 8, 9 However, like many other drugs used to treat cancer, the effectiveness of DOX has been limited by several obstacles, including the development of multidrug resistance during chemotherapy, dose-dependent side effects (bone marrow depression, cardiotoxicity, and congestive heart failure), nonspecific distribution, and short biological half-life.10, 11, 12, 13 A nanoparticle-based drug delivery system could potentially overcome these obstacles. The incorporation of the drug into nanoparticles (dimension below 200 nm) has a potential impact on its efficacy, so that decreases adverse cytotoxic effects, extends circulation time, increases solubility and stability of the drug, and increases the accumulation of the drug in the tumor vasculature via enhanced permeation and retention (EPR) effect.14, 15, 16, 17 Therefore, the development of intelligent nano-carriers for chemotherapeutic drugs is rapidly progressing to solve various limitations of conventional drug delivery systems.
