Abstract
Oxygen (O2) plays a critical role during photodynamic therapy (PDT), however, hypoxia is quite common in most solid tumors, which limits the PDT efficacy and promotes the tumor aggression. Here, a safe and multifunctional oxygen‐evolving nanoplatform is costructured to overcome this problem. It is composed of a prussian blue (PB) core and chlorin e6 (Ce6) anchored periodic mesoporous organosilica (PMO) shell (denoted as PB@PMO‐Ce6). In the highly integrated nanoplatform, the PB with catalase‐like activity can catalyze hydrogen peroxide to generate O2, and the Ce6 transform the O2 to generate more reactive oxygen species (ROS) upon laser irradiation for PDT. This PB@PMO‐Ce6 nanoplatform presents well‐defined core–shell structure, uniform diameter (105 ± 12 nm), and high biocompatibility. This study confirms that the PB@PMO‐Ce6 nanoplatform can generate more ROS to enhance PDT than free Ce6 in cellular level (p < 0.001). In vivo, the singlet oxygen sensor green staining, tumor volume of tumor‐bearing mice, and histopathological analysis demonstrate that this oxygen‐evolving nanoplatform can elevate singlet oxygen to effectively inhibit tumor growth without obvious damage to major organs. The preliminary results from this study indicate the potential of biocompatible PB@PMO‐Ce6 nanoplatform to elevate O2 and ROS for improving PDT efficacy.
Highlights
Because the Photodynamic therapy (PDT) process is dependent on O2 concentration, tumor hypoxia originating from the rapid tumor growth and abnormal tumor vessels[3,10,11] limits the efficacy of PDT and promotes therapeutic resistance and cancer progression.[12,13]
The transmission electron microscopy (TEM) image shows that the prussian blue (PB)@periodic mesoporous organosilica (PMO) presents a well-defined core–shell structure, demonstrating PB has been successfully coated with PMO (Figure 1a,b)
After conjugating amino and chlorin e6 (Ce6), the zeta potential of the PB@PMO changes to −23.4 ± 2.6 mV and −31.1 ± 2.3 mV, respectively, which is attributed to the positive charge of amino and the negative charge of Ce6 (Figure 1d)
Summary
Photodynamic therapy (PDT) has been proven to be a potential therapeutic strategy for cancers[1] via the reaction between photosensitizers and oxygen (O2) under laser to generate cytotoxic reactive oxygen species (ROS) for killing cancer cells.[2,3,4,5,6] Compared to traditional cancer therapy strategies, such as surgery, chemotherapy, and radiotherapy, PDT emerges as a promising treatment method with less invasiveness, fewer side effects, and higher selectivity and efficacy.[2,4,7,8,9] Because the PDT process is dependent on O2 concentration, tumor hypoxia originating from the rapid tumor growth and abnormal tumor vessels[3,10,11] limits the efficacy of PDT and promotes therapeutic resistance and cancer progression.[12,13]. We load a photosensitizer, chlorin e6 (Ce6), into periodic mesoporous organosilica coated prussian blue nanoparticles (PB@PMO) to develop an integrated, simple, and biocompatible platform for supplying O2 and generating singlet oxygen (1O2) for photodynamic therapy. The periodic mesoporous organosilica shell facilitates loading and delivering photosensitizers and the PB core can effectively catalyze H2O2 into O2 which sequentially receives the energy transferred by Ce6 from lasers to generate singlet oxygen for PDT. To the best of our knowledge, it is the first time to make use of the catalase-like activity of PB-based nanomaterials to enhance photodynamic therapy
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