Oh Seok Kwon^†‡∇, Hyun Seok Song^§∥∇, Joao Conde§⊥, Hyoung-il Kim^†, Natalie Artzi^*§#, and Jae-Hong Kim^*† 

 

^† Department of Chemical and Environmental Engineering, School of Engineering and Applied Science, Yale University, New Haven, Connecticut 06511, United States

^‡ BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong, Daejeon 305-600, Republic of Korea

^§ Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States

^∥ Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Yuseong, Daejeon 169-148, Republic of Korea

^⊥ School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, U.K.

^# Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States

 

^*Corresponding authors

^∇Author Contributions
O.S.K. and H.S.S. contributed equally to this work.

Abstract

Early diagnosis of tumor malignancy is crucial for timely cancer treatment aimed at imparting desired clinical outcomes. The traditional fluorescence-based imaging is unfortunately faced with challenges such as low tissue penetration and background autofluorescence. Upconversion (UC)-based bioimaging can overcome these limitations as their excitation occurs at lower frequencies and the emission at higher frequencies. In this study, multifunctional silica-based nanocapsules were synthesized to encapsulate two distinct triplet-triplet annihilation UC chromophore pairs. Each nanocapsule emits different colors, blue or green, following a red light excitation. These nanocapsules were further conjugated with either antibodies or peptides to selectively target breast or colon cancer cells, respectively. Both in vitro and in vivo experimental results herein demonstrate cancer-specific and differential-color imaging from single wavelength excitation as well as far greater accumulation at targeted tumor sites than that due to the enhanced permeability and retention effect. This approach can be used to host a variety of chromophore pairs for various tumor-specific, color-coding scenarios and can be employed for diagnosis of a wide range of cancer types within the heterogeneous tumor microenvironment.

 

Keywords:  upconversion; triplet-triplet annihilation; dual-color; nanocapsule; cancer; imaging; diagnosis