Catalase enzyme-modified carbon quantum dot nanoparticles with hypoxia alleviating, associated with indocyanine green for synchronous augmented photodynamic therapy and cell imaging of melanoma cancer

Abstract

The aim of this study was to synthesize carbon quantum dot nanoparticles (CQD NPs) with high quantum yield and conjugate it with catalase (CAT) enzyme for cell imaging and photodynamic therapy (PDT) application. CQD was synthesized by hydrothermal method and purified with a novel method to obtain high quantum yield. Indocyanine green (ICG) was loaded on the CQD as a proper photosensitizer for PDT and CAT enzyme was applied to generate oxygen in the tumor site. Then, the efficacy of the synthesized NPs for photodynamic therapy (PDT) and cell imaging of melanoma cancer cells was investigated at in vitro, ex vivo and in vivo environment. Characterization results confirmed that the hydrodynamic size of CAT-ICG@CQD particles were about 51.3 nm. In addition, the reactive oxygen species (ROS) detection analysis 1demonstrated that free ICG’s ROS generation capacity enhanced extremely (26%) after CAT conjunction. Moreover, cell culture assessments displayed that CAT-ICG@CQD could precisely decrease melanoma cell viability up to 15.66% laser illumination triggered in semitumor microenvironment resulting in higher cellular uptake, sustainable release and more ROS generation capacity in comparison to free ICG. Cell imaging analysis illustrated the high fluorescence intensity of ICG in cytoplasm for CAT-ICG@CQD, approving the high quantum yield and more ICG cell entrance than free ICG. The in vivo study on C57BL/6 mice containing melanoma cancer elucidated that CAT-ICG@CQD has superior inhibitory ability for the tumor growth by tumor oxygenation, implying efficient PDT with hypoxia alleviating. The outcome of the present study provided a novel nano-platform for ameliorating the tumor hypoxia, which meet demands of melanoma PDT by high efficiency of ROS generation and cell imaging capability.