No abstract

Hypoxia of solid tumor compromises the therapeutic outcome of photodynamic therapy (PDT) that relies on localized O 2 molecules to produce highly cytotoxic singlet oxygen (1 O 2) species. Herein, we present a safe and versatile self-assembled PDT nanoagent, i.e., OxgeMCC-r single-atom enzyme (SAE), consisting of single-atom ruthenium as the active catalytic site anchored in a metal-organic framework Mn 3 [Co(CN) 6 ] 2 with encapsulated chlorin e6 (Ce6), which serves as a catalase-like nanozyme for oxygen generation. Coordination-driven self-assembly of organic linkers and metal ions in the presence of a biocompatible polymer generates a nanoscale network that adaptively encapsulates Ce6. The resulted OxgeMCC-r SAE possesses well-defined morphology, uniform size distribution and high loading capacity. When conducting the in situ O 2 generation through the reaction between endogenous H 2 O 2 and single-atom Ru species of OxgeMCC-r SAE, the hypoxia in tumor microenvironment is relieved. Our study demonstrates a promising self-assembled nanozyme with highly efficient single-atom catalytic sites for cancer treatment.

No abstract

Photodynamic therapy (PDT), a wellknown clinical modality that involves photosensitizer, molecular oxygen (O 2 ), and excitation light to generate cytotoxic reactive oxygen species such as singlet oxygen ( 1 O 2 ), has been proven to be a selective method for treating a wide spectrum of localized and superficial cancers or other diseases. [1][2][3][4][5][6][7][8][9] In addition to destroying cancer cells through direct photodamage, PDT can also induce vascular damage in the tumor, and activate the response of immune system. [10][11][12][13] Possessing spatial and temporal control over the localization of the light irradiation, the O 2 -involved PDT can remarkably improve the selectivity and reduce the side effects when compared to other conventional modalities such as chemotherapy, surgery, and radiotherapy. [14][15][16] On the other hand, tumor hypoxia compromises therapeutic effect of PDT, as O 2 is an indispensable element during the process. Uncontrollable growth of tumor cells as well as dysregulated formation of tumor blood vessels inevitably result in the cancer hypoxia. [17,18] In addition, microvascular collapse caused by PDT would further compromise the O 2 supply and aggravate the hypoxia condition, thus preventing effective PDT of cancer. Consequently, a vicious circle occurs, as PDT not only consumes localized O 2 , but also cuts off the O 2 supply. [19][20][21] To date, three main strategies have been employed to overcome the pre-existing hypoxia and improve the therapeutic effect of PDT. The most popular approach relies on the integration of PDT with other therapeutic modalities for a synergistic therapy. [17,22,23] However, such complex structures are often costly, which limit their scalable production and reproducibility. Another strategy is the utilization of intelligent nanomaterials that can act as O 2 carriers for direct transportation of mole cular oxygen to tumor sites. For example, Hu and coworkers reported photosensitizer-loaded perfluorocarbon nanodroplets as an O 2 self-enriched PDT nanoplatform. [24] The last approach is to construct smart nanoplatforms for in situ generation of O 2 within solid tumors based on the characteristics Tumor hypoxia compromises the therapeutic efficiency of photodynamic therapy (PDT) as the local oxygen concentration plays an important role in the generation of cytotoxic singlet oxygen ( 1 O 2 ). Herein, a versatile mesoporous nanoenzyme (NE) derived from metal-organic frameworks (MOFs) is presented for in situ generation of endogenous O 2 to enhancethe PDT efficacy under bioimaging guidance. The mesoporous NE is constructed by first coating a manganese-based MOFs with mesoporous silica, followed by a facile annealing process under the ambient atmosphere. After removing the mesoporous silica shell and post-modifying with polydopamine and poly(ethylene glycol) for improving the biocompatibility, the obtained mesoporous NE is loaded with chlorin e6 (Ce6), a commonly used photosensitizer in PDT, with a high loading capacity. Upon the O 2 generation through the...