As a significant threat to public health, breast cancer is the most common tumor in women, with approximately 2.3 million new cases and 685,000 deaths worldwide in 2020 alone [1,2]. Breast cancer requires special attention due to its insufficient response to standard therapy [3]. Several therapies for breast cancer, including radiotherapy, chemotherapy, surgical procedures, and hormone therapy, have numerous side effects [4,5]. One of the most difficult tasks now facing chemotherapy, and the most used anti-cancer treatment method for tumor therapy, is represented by the controlled release of anti-tumor drugs targeted at a tumor area, as they are highly cytotoxic to normal cells. Chemotherapeutics are now delivered more effectively, which have raised their treatment impact. Increased availability and administration, drug accumulation to the tumor site, and harmless side effects have all been attained by employing nanomaterials as DD vectors [6]. Therefore, the establishment of nanocarriers with well-defined pores that are biodegradable, biocompatible, has a large loading capacity for various therapeutic, and can release pharmaceuticals in a regulated and sustained manner is necessary to build effective nanomedicines [7]. Clinical hyperthermia (HT) is defined as being exposed to temperatures between 39 and 45 °C [8]. Reaching these temperatures increases the blood flow to the tumor site, which makes it easier for medications and nanoparticles (NPs) to enter the otherwise difficult-to-penetrate tumor microenvironment [9]. One such instance that has shown useful for cancer therapy is the combination of chemotherapy with HT [10].

Soft magnetic substance nickel ferrite (NiFe2O4) has a high electric resistivity and a low magnetic coercivity and less magnetic anisotropy [11]. NiFe2O4 MNPs are superparamagnetic when their size is smaller than a critical diameter of around 30 nm [12], its structure is entirely flipped. All of the Ni2+ ions are arranged in octahedral orientations in this structure Fe3+, on the other hand, is distributed across octahedral and tetrahedral sites [13]. The NiFe2O4's spinal structure is a member of the Fd3m space group. The greatest options for magnetic hyperthermia (MHT) applications [14]; because of their medium magnetic moment, nearly zero remnant magnetization (Mr), chemical stability, biocompatibility, and comparatively high specific absorption rate (SAR) [15]. M. Khairy et al. [16] NiFe2O4 MNPs can be conjugated with drugs and are more suitable for cancer treatment; nickel-containing NPs are usually protected by lipids, polymers, and silica, they became more effective if liposomes encapsulated them [17]. Biocompatible materials that are commonly utilized for surface modification of NPs include polyethylene glycol (PEG), starch, chitosan, dextran, polyvinyl alcohol, lauric acid, oleic acid, and liposomes.

Liposomes are biomimetic vesicles increasingly examination in nanomedicine and pharmacology for diagnosis and treatment techniques [18], specifically in tumor treatment. The adjacent lipid bilayer offers the requisite systemic biocompatibility and preserves the magnetic properties of superparamagnetic iron oxide nanoparticles (SPIONs) from aggregation and oxidation [19]; it indicates a new form of magnetoliposomes (MLs). The encapsulating MNPs within liposomes also known as MLs had benefits. The aim is to magnetically guide the liposomes to a cancer and then create HT with an alternating magnetic field (AMF) [20,21]. MLs approach has additional benefits for lipid vesicles because it allows for selectively directing nano-systems to cancer via a magnetic range, increasing chemotherapeutic drug concentration on cancer, and effectively overheating tumor cells via an alternating magnetic field (AMF) [[22], [23], [24], [25]]. Ana et al. [12] reported that MLs were synthesized using NiFe2O4 NPs display a suitable size to biomedical applications, namely as antitumor drug nanocarriers with a simultaneous aptitude of HT. Irina et al. [17] NiFe2O4/Au were capsulated with a liposomes lipid bilayer, originating a liposome‐like structure, suitable for therapeutic applications and MLs nanosystems have the ability to create local thermal was assessed, proving their promising utility for thermotherapy applications.

Quercetin (QC) is for cancer therapy as chemotherapy and is the most critical natural dietary polyphenolic flavonoid, which is abundantly found in fruits and vegetables. According to studies, QC is a molecule that can prevent cancer by chemo-preventive impacts on cancer. It works by inhibiting the growth of cancer cells through several mechanisms such as anti-inflammatory, antioxidant, and apoptotic effects, as well as by modulating signal transduction pathways. MNPs significant be considered potential and optimizing nano-systems for delivering QC to cancer cells [26]. Therefore, it is anticipated that the synergistic effects of combining chemotherapy and MHT (chemo-hyperthermia) in the same nanocarrier-based MNPs may improve the efficacy of cancer treatment. Stefan et al. [27] in the absence of an AMF, the MLs loaded with doxorubicin (Dox) (Dox-MLs) demonstrated a toxic impact due to the passive release of small Dox quantity. When Dox-MLs exposed to AMF, it showed increased toxicity due to the release of more Dox quantity than to the previous ones. Natália et al. [19] the higher cytotoxicity in the tumor cells accompanied by a reduced toxic effect on the normal cells is considered an enhancing improvement in the treatment efficacy of Dox, when Dox is encapsulated in the ML. Alfonso et al. [20] a novel techniques and materials for thermosensitive MLs must be enhanced to create a good magnetic targeting effect, that stimulates thermal and thus ensures improved on-demand drug release (DR) and their internalization into cancer cells, decreasing drug distribution in normal cell. To our knowledge, the bio-combination of NiFe2O4@Liposome NPs with QC drug was not previously reported for chemotherapy/hyperthermia applications. Nonetheless, we investigated the use of HT in conjunction with chemotherapy since it provides the important benefit of requiring lower medication doses, resulting in an efficient treatment with fewer side effects and decreased drug resistance by cancer cells.

In this work, we have fabricated a novel NiFe2O4@Liposome magnetoliposomes (MLs) NPs biocompatible and quercetin (QC)-loaded MLs (QC-MLs) that were used to enhance the HT, chemo-hyperthermia, and drug delivery (DD). The SAR results showed that the synthesized MLs NPs with improved saturation magnetization (MS) and heating abilities. The drug loading (DL), encapsulation efficiency (EE), and drug controlled-release behaviors of free QC and QC-MLs were evaluated. Moreover, the in-vitro cytotoxicity effect of free QC, MLs, and QC-MLs hybrid systems were evaluated on MCF-7 cells.