Hypoxia mitigation by manganese-doped carbon dots for synergistic photodynamic therapy of oral squamous cell carcinoma
Frontiers in Bioengineering and Biotechnology(2023)
摘要
Photodynamic therapy (PDT) is widely used for cancer treatment due to its non-invasive and precise effectiveness, however, hypoxia in the tumor microenvironment greatly limits the efficacy of photodynamic therapy. Compared with conventional photosensitizers, carbon dots (CDs) have great potential. Therefore, developing a water-soluble, low-toxicity photosensitizer based on CDs is particularly important, especially one that can enhance the photodynamic efficacy using the tumor microenvironment to produce oxygen. Herein, manganese-doped carbon dot (Mn-CDs, ∼2.7 nm) nanoenzymes with excellent biocompatibility were prepared by a solvothermal method using ethylenediaminetetraacetic acid manganese disodium salt hydrate and o-phenylenediamine as precursors. TEM, AFM, HR-TEM, XRD, XPS, FT-IR, ζ potential, DLS, UV-Vis, and PL spectra were used to characterize the Mn-CDs. Cancer resistance was assessed using the CCK-8 kit, calcein AM versus propidium iodide (PI) kit, and the Annexin V-FITC/PI cell apoptosis assay kit. The obtained Mn-CDs have excellent near-infrared emission properties, stability, and efficient 1O2 generation. Notably, the manganese doping renders CDs with catalase (CAT)-like activity, which leads to the decomposition of acidic H2O2in situ to generate O2, enhancing the PDT efficacy against OSCC-9 cells under 635 nm (300 mW·cm−2) irradiation. Thus, this work provides a simple and feasible method for the development of water-soluble photosensitizers with oxygen production, presenting good biosafety for PDT in hypoxic tumors.
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关键词
acidic H2O2-driven oxygenator,manganese-doped carbon dots,photodynamic therapy,oral squamous cell carcinoma,tumor microenvironment
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