Female breast cancer (BC) was projected to surpass lung cancer as the most common tumor globally in 2020, with an estimated 2.3 million new cases, accounting for 11.7 % of all tumor diagnoses. BC ranks highest in both incidence and mortality in many countries [1]. Current BC treatments involve localized and regional therapies [2]. PTT has gained significant attention as a promising alternative to conventional tumor treatments. PTT utilizes a PT agent with strong light-to-heat conversion capabilities, which is delivered into cancer cells. Upon exposure to NIR irradiation, agent converts light into localized heat, leading to cancer cell inhibition or ablation through thermal damage [3]. PTT is a non-invasive, localized cancer therapy that utilizes NIR irradiation and often integrates light-triggered drug release (DR) [4]. Among novel two-dimensional (2D) NPs, Ti3C2Tx (MXene) has garnered considerable attention in the biomedical field due to its advantages, including low toxicity, good hydrophilicity, unique PT properties, and anticancer activity [[5], [6], [7], [8]]. X. Liu et al. [9] developed m-MXene/nHAp composites with biocompatibility, excellent drug-loading capacity, and PT properties, showing promise for repairing bone defects caused by bone tumors. Similarly, T. Liao et al. [10] reported the fabrication of an anti-cancer system using MXene@EGCG nanosheets with a particle size of approximately 243 nm and a high PT conversion efficiency (η) of 29.2 %. This system demonstrated significant cancer temperature elevation under NIR irradiation, highlighting its potential for effective tumor PTT.

Que, a flavonol found in various drinks, foods, and plants, can be effectively encapsulated in biodegradable polymer carriers to overcome its inherent limitations [11]. Shehab et al. [12] demonstrated that Que-magnetoliposome NPs, with enhanced DR rates and pH-dependent effects, significantly improved antitumor activity and chemo-hyperthermia, thereby increasing Que cytotoxicity and reducing the viability of MCF-7 BC cells. Zinc-based ZIF-8, a widely used metal-organic framework (MOF), possesses a large specific surface area along with strong chemical and thermal stability, making it a highly adaptable material. During synthesis, it can be modified to create a unique 3D internal space, enabling the incorporation of various biological macromolecules, preventing their leakage, and preserving their bioactivity. Additionally, ZIF-8 NPs have demonstrated potential as photo-responsive agents [[13], [14], [15]]. L. Zhan et al. [16] utilized ZIF-8 as a dual-drug nanocarrier, effectively inhibiting the proliferation of 4T1 breast cancer cells and reducing tumor growth by up to 70 %. B. Similarly, Li et al. [17] reported that MXene@Que nanocomposites exhibited exceptional energy conversion properties, achieving a high PT conversion efficiency (η) of 31 %. This resulted in significant cancer cell destruction, with a maximum proliferation reduction of 90 %. Integrating multiple functions into a single nanosystem can simplify and enhance the efficacy of tumor treatment.

Münteha et al. [18] reported the development of a pH-sensitive drug delivery system (DDS) was using 5-sulfosalicylic acid (5-SSA) and boswellic acids (BAs), which were loaded into ZIF-8 nanocomposites containing bovine serum albumin (BSA) as the core. The resulting 5-SSA/BSA@ZIF-8 and 5-SSA/BSA/BAs@ZIF-8 formulations demonstrated enhanced biocompatibility and therapeutic efficacy against MCF-7 cells while exhibiting minimal toxicity. Shatha et al. [19] established a pH-sensitive multifunctional DDS by incorporating gemcitabine hydrochloride (Gem) and amygdalin (Amy) into a BSA-centered ZIF-8, forming BSA-Gem@ZIF-8 and BSA-Gem-Amy@ZIF-8 NPs. These nanocomposites were further coated with polydopamine (Dopa), chelated by Au3+, and conjugated with gallic acid (GA), resulting in BSA-Gem@ZIF-8/Dopa/GA and BSA-Gem-Amy@ZIF-8/Dopa/GA. The final formulations demonstrated enhanced cytotoxicity and apoptotic effects against MCF-7 cells while exhibiting lower toxicity in HUVEC control cells. The special characteristics of MOFs, particularly exemplified by ZIF-8, hold high promise in overcoming existing challenges associated by DDS, presenting a compelling avenue for the establishment of efficient and targeted treatment interventions [20]. In our study, we developed a hybrid nanosystem by conjugating MXene with ZIF-8-MOF and encapsulating it in liposomes (LPs), forming Que-loaded MX-ZIF-8@LPs (Que-MX-ZIF-8@LPs) nanocomposites. The goal was to create multifunctional nanocarriers for DD and PTT, offering more comprehensive treatment options for BC, both in vitro and in vivo.

In this work, we present a smart drug delivery (SDD) system based on MXene integrated with ZIF-8, in which the antitumor drug Que is loaded into MX-ZIF-8 and encapsulated in liposomes, forming Que-MX-ZIF-8@LPs nanocomposites. We evaluated the N2 adsorption–desorption, cumulative pore volume, pore size distributions (PSD), and XPS analyses of the Que-MX-ZIF-8@LPs nanocomposite. The drug loading (DL), encapsulation efficiency (EE), and kinetics release under NIR were measured. Molecular docking studies provided moderate binding strengths of MX-ZIF-8 NPs to tumor-related protein targets (Akr1b1) and Que indicated even higher interactions. Molecular docking interactions between ZIF-8 and MXene suggest complementary roles in Que-MX-ZIF-8@LPs nanocomposites, enhancing their overall stability and therapeutic effectiveness. Our findings indicate that these nanocomposites can improve tumor cell treatment with combining controlled DR with increased cellular sensitivity to treatment. We will evaluate their in vitro efficacy, including cytotoxicity utilizing the MTT assay, flow cytometry, and cellular uptake, as well as their anticancer effects in vivo through xenograft experiments in nude mice under NIR.