Recently, photodynamic therapy (PDT) has been deemed to be the most promising strategy for cancer treatment. To improve the efficacy for PDT, nanocarriers are expected to target mitochondria that are vulnerable to toxic reactive oxygen species (ROS). Moreover, overcoming tumor hypoxia is also conducive to enhance the PDT efficacy. Upconversion nanoparticles (UCNPs) can convert near infrared (NIR) light to visible light, thus stimulating photosensitizers to effectively produce cytotoxic ROS and achieving a high tissue penetration depth. In this study, a multifunctional nanocarrier UCNPs@G4/Ce6/CAT-CTPP was synthesized by a novel thiol-ene and azide-acetylene click reaction route to connect the original oleic acid ligands and dendrimers. Interestingly, the constructed “hydrophobic and hydrophilic pockets” around one single upconversion nanoparticle can simultaneously load hydrophobic photosensitizer Chlorin e6 (Ce6) and hydrophilic catalase (CTA) for catalytic enhanced PDT activated by NIR laser. Also, the mitochondrial targeting molecules (3-carboxypropyl) triphenylphosphonium bromide (CTPP) were modified outside of the dendrimers to efficiently target mitochondria. Both the catalytic degradation of hydrogen peroxide (HO) by catalase to overcome tumor hypoxia and mitochondrial targeting greatly enhance the efficacy of PDT. More importantly, this system provides a new paradigm for designing inorganic nanocrystal core and dendrimer shell for cargo delivery.Copyright © 2020 Elsevier Ltd. All rights reserved.
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