A versatile Pt-Ce6 nanoplatform as catalase nanozyme and NIR-II photothermal agent for enhanced PDT/PTT tumor therapy
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Published online 9 September 2020 | https://doi.org/10.1007/s40843-020-1431-5
A versatile Pt-Ce6 nanoplatform as catalase nanozyme and NIR-II photothermal agent for enhanced PDT/PTT tumor therapy 1†
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Qing Chen , Su He , Fangjun Zhang , Fengzhi Cui , Jianhua Liu , Man Wang , Dongmei Wang , 1* 1,2* Zhigang Jin and Chunxia Li ABSTRACT The hypoxic nature of solid tumors has severely negative effects on oxygen-based photodynamic therapy. In this study, we used porous Pt nanoparticles as a catalase (CAT) nanozyme, the second near-infrared (NIR-II) region photothermal transition agents (PTAs), and carriers of photosensitizer chlorin e6 (Ce6) to synthesize a composite nanosystem Pt-Ce6. In this system, Pt-Ce6 can continuously and stably decompose H2O2 into oxygen, thereby alleviating tumor hypoxia and improving the effect of photodynamic therapy (PDT). With 650 nm illumination, the reactive oxygen species (ROS) produced by Ce6 will decrease the mitochondrial membrane potential (MMP, ΔΨm) to release cytochrome c (Cyt-c) from the mitochondria into the cytoplasm, eventually leading to mitochondrial-mediated cellular apoptosis during the PDT process. In addition, Pt-Ce6 has good photothermal stability and high photothermal conversion efficiency (52.62%) in the NIR-II region. In U14 tumor-bearing mice, Pt-Ce6 completely suppressed tumor growth and recurrence under laser irradiation. Thus the nanocomposite shows excellent PDT/photothermal therapy (PTT) synergistic performance in vitro and in vivo. Keywords: hypoxia, catalase, photodynamic, photothermal therapy, cell apoptosis mechanisms
INTRODUCTION Hypoxia is one of the basic hallmarks of most solid tumors owing to insufficient blood flow, irregular cancer cell proliferation and inadequate endogenous oxygen, which will resist the therapeutic outcomes of the oxygen-
dependent therapy modes including photodynamic therapy (PDT) and radiotherapy (RT), sonodynamic therapy (SDT), and immunotherapy [1–5]. In particular, PDT acting as a non-invasive, specific and controllable treatment has been extensively studied [6–12]. However, the strong dependence of PDT on molecular oxygen severely handicaps its effective application in low-oxygen environment [13,14]. So far, various strategies have been developed to overcome tumor hypoxia, which can generally be divided into three categories. (i) Using O2-carrying molecules. Perfluorocarbon, fluorocarbon-chain and perfluoropentane have high affinity to O2 and can dissolve large amount of O2 and directly deliver O2 into tumor to boost the oxygenation degree [15–19]. (ii) Using O2-generating nanomaterials such as CaO2 via chemical decomposition reaction [20,21]. (iii) Using natural catalase (CAT) or CAT-like nanomaterials such as MnO2, C3N4, metal-organic frameworks (MOFs) and noble metal nanoparticles [22–27]. Compared with the former two, the third one mainly utilize the tumor microenvironment (TME) to catalyze endogenous H2O2 to in situ generate O2, which consumes the undesirable tumor metabolites (H2O2) without causing si
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