## 1 Introduction  
Breast cancer is now the world's most prevalent cancer, according to statistics from the International Agency for Research on Cancer (IARC) [1; 2; 3; 4]. The experts at the World Health Organization (WHO) revealed that 2.3 million women worldwide were diagnosed with breast cancer in 2020, and 685,000 died from it. Nowadays, 1 in 5 individuals around the world will develop one type of cancer in their lifetime [5; 6; 7; 8]. Among them, breast cancer is a major public health problem in both developed and developing countries. The high mortality rate caused by breast cancer is due to its high rate of metastasis [9; 10; 11; 12]. Conventional treatment consists of surgery and radiation therapy. In order to reduce the risk of metastasis, systemic therapy is recommended. Doxorubicin (DOX) belongs to the anthracycline family of antibiotics. Since its introduction in the early 1970s, doxorubicin has been generally considered the leading dynamic chemotherapeutic agent in the treatment of metastatic breast cancer [13]. However, DOX has several adverse effects due to its lack of selectivity with subsequent treatment failure. Furthermore, DOX has been reported to cause cardiotoxicity, acute nausea, vomiting, alopecia, stomatitis, or reactions [14; 15; 16]. The development of drug delivery systems has been employed to overcome several major issues of conventional systems. Thus, the lack of drug solubility, the targeted control of drug release, or increasing the circulating time are several main issues to be addressed. In addition, the toxicity should be reduced, or the immunogenicity minimized [17; 18; 19]. This fact is highly associated with non-selective or non-specific damage to healthy tissue [20; 21]. Appropriate drug delivery is a key component to achieving an efficient drug recovery response. Recently, nanotechnology has been considered a powerful tool for creating carriers for specific molecules. Its role is to improve the stability, bioavailability, and pharmacokinetic profile of drugs and reduce their toxicity [22; 23]. Nanocarriers and innovative formulations play a tremendous role in enhancing the drug's bioavailability and healing potential. This fact ensures the drug availability at the target site [24]. However, nanocarriers find numerous issues generated by the tumor microenvironment, such as acidity, hypoxia, abnormal temperature, or protein/enzyme levels. Therefore, these major issues can be managed by tailoring the physical and chemical properties of ongoing delivery systems [20; 25]. In comparison to healthy tissue, tumor tissue exhibits a higher temperature, which represents a way to control the drug release by an external heating source [26; 27]. The presence of inorganic nanoparticles besides the polymeric thermo-sensitive shell is beneficial. This will ensure a higher capacity to respond to external heating sources, reaching the required temperature [28; 29; 30]. Poly(N-isopropylacrylamide) (PNIPAM) is a thermo-sensitive water-soluble polymer that has been used to incorporate and release certain types of chemotherapeutic drugs. Thus, PNIPAM is part of a class of environmentally responsive biomaterials able to manifest changes in concordance with environmental stimuli (light, pH, ions, temperature, electric field, etc.) [31; 32; 33; 34]. PNIPAM chains undergo conformational transitions in an aqueous solution in response to temperature. The lower critical solution temperature (LCST) of 32-34 \({}^{\circ}\)C for this \"smart polymer\" has made it useful for various applications such as valves and sensors, cell culture media, membranes, and drug delivery systems [35; 36; 37; 38]. Numerous PNIPAM nanocarriers have been developed as candidates for use in biomedical applications [39; 40; 41; 42; 43]. The combined assembly of stimuli-responsive polymers with inorganic magnetic nanoparticles could exhibit properties for controlled delivery of doxorubicin into biological targets.