Journal
BIOMATERIALS
Volume 153, Issue -, Pages 14-26Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.10.034
Keywords
Photodynamic therapy; Mitochondria targeting; Graphene quantum dots; Rare-earth upconversion nanoparticles; Singlet oxygen
Funding
- National Natural Scientific Foundation of China (NSFC) [81630046]
- NSFC Project of International Cooperation and Exchanges [61361160414]
- NSFC [21674040, 51403042]
- Natural Science Foundation for Distinguished Young Scholars of Guangdong Province [2016A030306013]
- Guangdong Program for Support of Top-notch Young Professionals [2015TQ01R604]
- Natural Science Foundation of Guangdong Province [2014A030310310]
- Scientific Research Projects of Guangzhou [201607010328]
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Photodynamic therapy (PDT) has been proposed in cancer treatment for decades, but its clinical translation is significantly impeded by the low yield of ROS, poor tissue penetration depth of most current photosensitizers, and short lifetime of ROS. These limitations directly affect the therapeutic effect of PDT in cancer therapy. Here we proposed a new strategy by collaboratively integrating rare-earth doped upconversion nanoparticles (UCNP) with graphene quantum dot (GQD) for highly efficacious PDT, based on the merits of UCNP, which can emit UV-vis light under near-infrared light (NIR) excitation, and GQD, which can produce O-1(2) efficiently. For GQD-decorated UCNP nanoparticles (UCNP-GQD), the emission light from UCNP can further excite GQD with prominent O-1(2) generation for NIR-triggered PDT. Furthermore, a hydrophilic rhodamine derivative, TRITC, is covalently tethered to afford the resultant UCNP-GQD/TRITC, possessing distinct mitochondrial targeting property. Thus mitochondrial specific PDT with in-situ O-1(2) burst in mitochondria induces sharp decrease of mitochondrial membrane potential, which initiates the tumor cell apoptosis irreversibly. Importantly, in vivo experiments demonstrate the tumor inhibition of mitochondrial targeting UCNP-GQD/TRITC with improved therapeutic efficiency compared with non-targeting UCNP-GQD. The proposed strategy highlights the advantages of precision organelles-specific PDT in cancer therapy. (C) 2017 Elsevier Ltd. All rights reserved.
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