Cancer is a detrimental disease worldwide. Various therapeutic approaches were investigated. Chemodynamic therapy (CDT) is an intense therapeutic approach triggered due to the formation of reactive oxygen species (ROS) in the tumor region through Fenton and Fenton-like reaction (Tang et al., 2019, Wu et al., 2021; Sun et al., 2022b;Han et al., 2021, Deinavizadeh et al., 2022). It is a chemical in situ process that is triggered by endogenous causes, that is rapidly associated with an acidic pH and a high hydrogen peroxide (H2O2) content. The ROS consist of singlet oxygen (1O2), superoxide anions (O2−.), H2O2, and hydroxyl (∙OH) radical. Oxidative stress occurs when there is an excessive synthesis of ROS, leading to damage to DNA, proteins, nucleic acids, and lipids. Oxidative stress induces the deterioration and demise of cancer cells (Zheng et al., 2020, Wang et al., 2021, Wan et al., 2020, Yang et al., 2017). The Fenton reaction is a therapeutic strategy that can enhance the generation of ROS to damage the cancer cells. Tumor cells have higher levels of H2O2 in comparison to normal cells (Wu et al., 2018). The Fenton reaction utilises Fe2+/Fe3+ as a catalyst that involves catalytic decomposition of endogenous H2O2 to the produce detrimental ∙OH at the tumor site, hence augmenting the effectiveness of the CDT effect (Hou et al., 2019). Furthermore, the ∙OH possess an intense oxidation potential that can oxidize and damage tumor cell organelles, resulting in cell death.

Photothermal therapy (PTT) is a non-invasive strategy that can convert optical energy to thermal energy (heat) (Wu et al., 2018, Zhou et al., 2019, Xu et al., 2019, Chen et al., 2021, Pan et al., 2022, Deinavizadeh et al., 2021). The PTT advantages comprise of high selectivity, temporal, and spatial resolution, excellent photothermal stability, enhance conversion efficiency, good biocompatibility and minimal toxicity (Chen et al., 2020; Liu et al., 2022a Cai et al., 2011, Xu et al., 2021, Wu et al., 2021, Liu et al., 2020, Lee et al., 2022). The PTT can generate high thermal energy cancer cells to cause cancer cell apoptosis while inflicting no harm to the normal cells. Another an effective therapeutic approach for treating cancer is chemotherapy. However, chemotherapy treatment has many limitations such as lack of drug resistance in tumor sites, significant drug leakage, low efficiency of drug loading, and insufficient specificity (Yang et al., 2020; Wang et al., 2020b)). PTT can be exploited to enhance Fenton reaction rate and drug release efficiency through synergistic manner that promotes CDT effect and chemotherapy (Sun et al., 2022a; Mendes et al., 2017). Therefore, the combined therapeutic strategies hold potential for significantly enhancing curative efficacy and mitigating challenges (Wang et al., 2020a; Qi et al., 2020a; Deinavizadeh et al., 2023).

Near-infrared (NIR) fluorescence has been extensively employed in the bioimaging with intense tissue transparency within the biological windows wavelength (600–1100 nm) owing to the enhanced deep tissue penetration ability, minimal phototoxicity and photo damage effect, good biocompatibility and non-invasiveness (Zhao et al., 2023, Chen et al., 2014, Zhao et al., 2018). Upconversion nanoparticles (UCNPs) can convert NIR light to the UV/Vis light that generates enhanced anti-stroke luminescence (Dash et al., 2023, Dash et al., 2024). UCNPs have significant promise for several applications including bioimaging, theranostics, biosensing, drug delivery, photovoltaic cells, data storage and photocatalysis applications due to high physical/chemical stability, tunable optical properties, non-blinking, non-autofluorescence background interference, minimal biological tissue damage and phototoxicity, enhance tissue penetration depth, good biocompatibility and high signal-to-noise ratios (Lee et al., 2022, Chen et al., 2014, Yang et al., 2019, Yuan et al., 2015, Ling et al., 2022; Lv et al., 2019b; Deng et al., 2011; Wang et al., 2020c; Chan et al., 2016). The combination of UCNPs with photosensitizers (PSs) can enhance ROS generation and upconversion luminescence efficiency under NIR laser irradiaon (Chu et al., 2022; Hou et al., 2015b; Feng et al., 2016). The integration of UCNPs and photocatalysts nanomaterials enhance the fluroscence resonance energy transfer (FRET) efficiency for cancer treatment (Choi et al. 2021). The photocatalytic materials including TiO2, ZnO, Fe3O4, g-C3N4, WO3, and Cu2O displays possess enhanced chemical stability, intense catalytic activity, and electron-hole pair separation (Patra et al., 2023, Arumugam et al., 2020, Yang et al., 2015, Chen et al., 2020, Reddy and Kim, 2020, Yusoff et al., 2015). The combination of UCNPs and photocatalytic materials can exhibit high therapeutic efficacy for cancer treatment. Magnetic iron oxide (Fe3O4) nanoparticles possess low cost, good chemical stability, high surface area, enhanced magnetic resonance imaging (MRI) effect, superior catalytic activity, excellent T2 contrast agent for MRI, magnetic targeting drug delivery, high magnetic separation, good biocompatibility and exceptional photothermal effect (Beigi et al., 2022, Muzzi et al., 2022; Liu et al., 2022b; Xu et al., 2022a; Liang et al., 2021b; Wang et al., 2019; Lv et al., 2019a; Zhao et al., 2020). Therefore, it has great attention for therapeutic approach and multimodal bio-imaging for cancer treatment. Moreover, Fe3O4 nanoparticles have great attention for the Fenton reaction owing to presence of both Fe2+ and Fe3+ ions (Thirumurugan et al., 2024; Xu et al., 2022b).

Mesoporous silica nanoparticles are remarkable for biomedical applications due to the intense catalytic activities, photothermal activity, high hydrophilicity, ease of surface functionalization, substantial pore capacity, adjustable pore dimensions, and specific surface area, good biocompatibility, ample cellular uptake, chemical stability, intense drug loading efficiency and low cost and enhance free diffusion of products and/or reactants (Huo et al., 2017, Gowsalya et al., 2022, Ang et al., 2021, Estevão et al., 2022, Trukawka et al., 2020, Deinavizadeh et al., 2024). The combination of magnetic nanoparticles and mesoporous nanoparticles could effiectively enhance separation that have great attention in varius field including therapeutic approch, biosensor, diagonosis, and drug delivery (Liu et al., 2019; Hou et al., 2015a). Further, the combination UCNPs with magnetic mesoporous nanoparticles can decompose H2O2 to produce intense ROS through Fenton reaction that can kill the cancer cells. Nonetheless, there has been limited investigation using these nanocomposites through combinational therapeutic CDT, PTT, and chemotherapy effects. Wu et al. synthesized core–shell structure of Fe3O4-polypyrrole (Fe3O4@PPy) and further modified with PEG to enhance blood biocompatibility and stability (Wu et al., 2018). Thus, the Fe3O4@PPy-PEG nanoparticles possess intense ROS generation and photothermal properties through the synergistic therapeutic effect under NIR irradiation based on the Fenton reaction for cancer theranostic treatment. The Fe3O4 coated onto the MnO2 nanoparticles that are doped with UCNPs (MUCNPs) and black phosphorous nanosheets (BPNs) nanoparticles that are loaded with photosensitizer chlorin e6 (Ce6) to form MUCNPs@BPNs-Ce6 nanocomposites (Zhang et al., 2020a). The nanoparticles exhibited excellent photothermal performance, enhanced ROS generation, and intensified dual modal (T1 & T2) magnetic resonance imaging activities through the synergistic PDT/PTT theranostics effect for cancer treatment.

Herein, Fe3O4 nanoparticles are incorporated into mesoporous silica (mS) layer, which were further decorated onto the surface of the UCNPs as a core material (UCNP-Fe3O4@mS, FMUP). Methotrexate (MTX) an anticancer drug was loaded onto mS to form FMUP-MTX nanocomposite. Further, the nanocomposites’ physiochemical properties were evaluated including photothermal properties, MRI, and hydroxy radical generation. The MTX based nanocomposite’s in vitro and in vivo analysis was performed under NIR 808 nm laser. The overview of this work including materials synthesis are presented in Scheme 1.