Upconversion superballs for programmable photoactivation of therapeutics

Zhen Zhang, Muthu Kumara Gnanasammandhan Jayakumar, Xiang Zheng, Swati Shikha, Yi Zhang, Akshaya Bansal, Dennis J. J. Poon, Pek Lim Chu, Eugenia L. L. Yeo, Melvin L. K. Chua, Soo Khee Chee and Yong Zhang ()
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Zhen Zhang: National University of Singapore
Muthu Kumara Gnanasammandhan Jayakumar: National University of Singapore
Xiang Zheng: National University of Singapore
Swati Shikha: National University of Singapore
Yi Zhang: National University of Singapore
Akshaya Bansal: National University of Singapore
Dennis J. J. Poon: National Cancer Centre Singapore
Pek Lim Chu: Duke-NUS Medical School
Eugenia L. L. Yeo: National Cancer Centre Singapore
Melvin L. K. Chua: National Cancer Centre Singapore
Soo Khee Chee: Duke-NUS Medical School
Yong Zhang: National University of Singapore

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Upconversion nanoparticles (UCNPs) are the preferred choice for deep-tissue photoactivation, owing to their unique capability of converting deep tissue-penetrating near-infrared light to UV/visible light for photoactivation. Programmed photoactivation of multiple molecules is critical for controlling many biological processes. However, syntheses of such UCNPs require epitaxial growth of multiple shells on the core nanocrystals and are highly complex/time-consuming. To overcome this bottleneck, we have modularly assembled two distinct UCNPs which can individually be excited by 980/808 nm light, but not both. These orthogonal photoactivable UCNPs superballs are used for programmed photoactivation of multiple therapeutic processes for enhanced efficacy. These include sequential activation of endosomal escape through photochemical-internalization for enhanced cellular uptake, followed by photocontrolled gene knockdown of superoxide dismutase-1 to increase sensitivity to reactive oxygen species and finally, photodynamic therapy under these favorable conditions. Such programmed activation translated to significantly higher therapeutic efficacy in vitro and in vivo in comparison to conventional, non-programmed activation.

Date: 2019
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DOI: 10.1038/s41467-019-12506-w

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