Isoliquiritigenin-infused electrospun nanofiber inhibits breast cancer proliferation and invasion through downregulation of PI3K/Akt/mTOR and MMP2/9 pathways

Breast cancer (BC) is the most common cancer among women worldwide. Despite the use of adjuvant strategies such as radiotherapy alone or in combination with chemotherapy after tumor resection, most deaths caused by BC result from tumor recurrence [1]. Adjuvant therapy can also cause severe adverse effects. Therefore, the focus is on developing more effective approaches in the absence of adequate preventive therapies for BC recurrence [2]. Various methods have been adopted to prevent cancer recurrence [3]. Drug-eluting implants offer a promising strategy for limiting cancer recurrence by minimizing off-target drug distribution and providing localized and prolonged chemotherapeutic delivery to on-target sites [4,5]. Implantable systems, including polymeric films, sponges, and injectable hydrogels, have been utilized for this purpose [6].

Electrospinning is a versatile and effective method for producing nanofibers for biomedical applications, particularly drug delivery systems [7]. Material preparation has made significant progress in nanofiber engineering and is widely recognized and used in tissue engineering, membranes, wound dressings, reinforcement, and layered tissue [[8], [9], [10]]. Various methods for scaffold production have been recently explored [11,12]. Nanofibers can be made from a range of materials, with the choice of material depending on the intended use of the fabric. These structures have unique properties such as high drug loading, mechanical strength, controlled release kinetics, and improved stability. Researchers have focused on nanofiber scaffolds as wound dressings to promote wound healing and reduce tumor size, inhibit cancer cell growth, and prolong the life of tumor-bearing animals [13,14]. Naturally derived materials are preferred for nanofiber scaffolds [15]. Nanofibers offer several advantages in cancer treatment, including fibers with diameters ranging from nanometers to submicrometers. They also offer surface modification, orientation variation, and drug encapsulation. Electrospun nanofibers have numerous applications due to these properties. Nanofibers loaded with anticancer drugs can facilitate controlled and sustained drug release at the site of action with increased efficacy. Additionally, nanofibers have been used as implants in biomaterials to prevent tumor recurrence and extend drug release at the tumor site. Moreover, nanofibers can create cellular environments that mimic the tumor microenvironment in vivo.

Isoliquiritigenin (ISL), a dietary flavonoid also known as 2′,4,’ 4-trihydroxy chalcone, has been proven to effectively combat BC proliferation through various mechanisms such as inhibiting the cell cycle, angiogenesis, proliferation, metastasis, and inducing apoptosis [[16], [17], [18], [19]]. In numerous in vitro and in vivo studies, ISL has shown to inhibit the growth of many types of cancer. Our laboratory has previously reported on the molecular mechanisms that underlie ISL's anti-cancer properties [[20], [21], [22]]. The anti-BC efficacy of ISL is limited by its hydrophobic nature, low bioavailability, and susceptibility to rapid degradation and instability in aqueous media, as well as its rates of absorption and elimination. These factors collectively contribute to the diminished effectiveness of ISL in combating BC. Thus, this study aims to create electrospun ISL-nanofiber scaffolds (ISL-NF) to inhibit the invasive and migratory capacity of BC cells.

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