Cancer is currently one of the major obstacles preventing the reduction of the global mortality rate[1, 2]. Traditional cancer treatment strategies, such as chemotherapy, radiation therapy, and surgery, result in unavoidable side effects, the development of drug resistance, and ineligibility for surgery [3–5]. The limitations of these treatments have motivated researchers to develop new cancer treatments with relatively few side effects and a high efficiency. Near-infrared light (NIR)-induced tumor therapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), have attracted the attention of many researchers because they are highly effective, non-invasive, spatiotemporally controllable, and lead to relatively few side effects [6, 7].
PDT involves the absorption of photon energy by a photosensitizing agent (PSA), resulting in the transfer of its electrons to the oxygen molecules (O2) in the cancer cells. This leads to the production of a highly toxic reactive oxygen species (ROS, e.g., 1O2) that cause irreparable damage to the cancer cells [8]. A light operative dose, reasonable PSA concentration, and adequate oxygen are necessary for effective tumor ablation. In addition, the amount of O2 directly affects the efficiency of PDT [9]. Due to the rapid and uncontrolled proliferation of tumor cells, the O2 levels in solid tumors are inadequate, thereby reducing the therapeutic efficiency of PDT [10, 11]. Thus, researchers have proposed innovative strategies to enhance the O2 concentration in tumors [12]. Oxygen carriers, such as perfluorocarbon (PFC) nanoparticles NPs, can facilitate continuous oxygen supply and have been used to enhance the O2 concentration in tumors for PDT [13]. Enzyme-like substances with catalase activity have recently been used with PSA to counter hypoxia and enable ROS generation [14]. Researchers have discovered that the overexpression of H2O2 in a tumor microenvironment (TME) can be utilized for the catalytic generation of endogenous O2 and facilitate tumor PDT [15, 16]. Nanoenzymes, in comparison with natural catalase, have a relatively low cost, high activity, and qualified thermostability. Therefore, they can be employed to enhance the therapeutic effect of PDT [17–19].
PTT is an alternative phototherapy technique that can utilize the photothermal effects of photothermal transduction agents (PTAs) to raise the temperature of the surrounding environment and trigger the ablation and apoptosis of cancer cells [20, 21]. The application of a PTA with high biocompatibility and efficient photothermal conversion efficiency is likely to improve the efficiency of photothermal therapy [22]. Several PTAs, such as two-dimensional (2D) materials [23], noble metal materials [24], metal chalcogenide materials [25], and conjugated polymers (e.g., polydopamine (PDA) and polypyrrole (PPy)), have been synthesized in recent years [26, 27].However, owing to the poor performance of a single PTA, high-energy NIR laser irradiation or a relatively strong dose of PTA is required to obtain the desired treatment effect[28]. In addition, it is difficult to achieve satisfactory therapeutic activity by solely using PTT[29]. Thus, modern studies are focusing on dual-mode therapy combinations of PTT and PDT [30, 31]. The main obstacle involves building a reasonable nanoplatform to maximize the synergistic effects of PTT and PDT to kill tumor cells.
The application of iridium oxide (IrO2) has recently drawn attention due to its high biocompatibility and photothermal conversion efficiency [32]. Studies have discovered that IrO2 has catalase (CAT)-like activity that enables it to catalyze H2O2 in the TME to generate endogenous O2, thereby enhancing the efficiency of PDT [33]. However, few studies have utilized IrO2 nanomaterial-based nanoplatform systems for the combined PTT and PDT treatment of tumors. An IrO2@[email protected] nanocomposite was synthesized in this study for the PTT and PDT dual-mode therapeutic treatment of tumors. IrO2 was prepared by a simple hydrolysis method and coated with a thin layer of mesoporous silica (MSN) to facilitate the physical adsorption of Chlorin e6 (Ce6). Subsequently, PDA was coated on the surface of IrO2@MSN, followed by the grafting of bovine serum albumin (BSA) on the surface of IrO2@[email protected] as a stabilizer. The installation of IrO2@[email protected] (Ce6) serves several purposes. The PDA coating and IrO2 NPs demonstrate significant photothermal conversion under NIR irradiation. IrO2@[email protected](Ce6) can produce ROS to kill cancer cells under photon activation. IrO2 can also catalyze the decomposition of H2O2 to enhance the production of O2 in the TME, thereby enhancing the therapeutic effect of PDT. In vitro and in vivo experiments have proved that IrO2@[email protected](Ce6) is biocompatible and can passively target tumors through the enhanced permeability and retention (EPR) effect, thereby harnessing the clinical and synergistic effects of PTT and PDT for the tumors. The design of IrO2@[email protected](Ce6) provides a framework for the design of multifunctional nanocomposites that can accurately treat cancer.