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Nanomaterials 2017, 7(9), 269; doi:10.3390/nano7090269

Near-Infrared-Triggered Photodynamic Therapy toward Breast Cancer Cells Using Dendrimer-Functionalized Upconversion Nanoparticles

1
Division of Thoracic Surgery, Department of Surgery, Changhua Christian Hospital, Changhua County 50006, Taiwan
2
School of Medicine, Chung Shan Medical University, Taichung City 40201, Taiwan
3
Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung City 40227, Taiwan
4
School of Medicine, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan
5
Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung City 40201, Taiwan
6
Department of Biomedical Sciences, Chung Shan Medical University, Taichung City 40201, Taiwan
7
Department of Medical Education, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 3 August 2017 / Revised: 4 September 2017 / Accepted: 7 September 2017 / Published: 11 September 2017
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Abstract

Water-soluble upconversion nanoparticles (UCNPs) that exhibit significant ultraviolet, blue, and red emissions under 980-nm laser excitation were successfully synthesized for performing near infrared (NIR)-triggered photodynamic therapy (PDT). The lanthanide-doped UCNPs bearing oleate ligands were first exchanged by citrates to generate polyanionic surfaces and then sequentially encapsulated with NH2-terminated poly(amido amine) (PAMAM) dendrimers (G4) and chlorine6 (Ce6) using a layer-by-layer (LBL) absorption strategy. Transmission electron microscopy and X-ray diffraction analysis confirm that the hybrid UCNPs possess a polygonal morphology with an average dimension of 16.0 ± 2.1 nm and α-phase crystallinity. A simple calculation derived through thermogravimetric analysis revealed that one polycationic G4 dendrimer could be firmly accommodated by approximately 150 polyanionic citrates through multivalent interactions. Moreover, zeta potential measurements indicated that the LBL fabrication results in the hybrid nanoparticles with positively charged surfaces originated from these dendrimers, which assist the cellular uptake in biological specimens. The cytotoxic singlet oxygen based on the photosensitization of the adsorbed Ce6 through the upconversion emissions can be readily accumulated by increasing the irradiation time of the incident lasers. Compared with that of 660-nm lasers, NIR-laser excitation exhibits optimized in vitro PDT effects toward human breast cancer MCF-7 cells cultured in the tumorspheres, and less than 40% of cells survived under a low Ce6 dosage of 2.5 × 10−7 M. Fluorescence microscopy analysis indicated that the NIR-driven PDT causes more effective destruction of the cells located inside spheres that exhibit significant cancer stem cell or progenitor cell properties. Moreover, an in vivo assessment based on immunohistochemical analysis for a 4T1 tumor-bearing mouse model confirmed the effective inhibition of cancer cell proliferation through cellular DNA damage by the expression of Ki67 and γH2AXser139 protein markers. Thus, the hybrid UCNPs are a promising NIR-triggered PDT module for cancer treatment. View Full-Text
Keywords: upconversion; dendrimers; photodynamic therapy; layer-by-layer; cancer stem cells; near-infrared; tumorspheres upconversion; dendrimers; photodynamic therapy; layer-by-layer; cancer stem cells; near-infrared; tumorspheres
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wang, B.-Y.; Liao, M.-L.; Hong, G.-C.; Chang, W.-W.; Chu, C.-C. Near-Infrared-Triggered Photodynamic Therapy toward Breast Cancer Cells Using Dendrimer-Functionalized Upconversion Nanoparticles. Nanomaterials 2017, 7, 269.

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