Versatile and Finely Tuned Albumin Nanoplatform based on Click Chemistry

Albumin is one of the most attractive nanoplatforms for targeted imaging and drug delivery due to its biocompatibility and long circulation half-life. However, previously reported albumin-based nanoplatforms have shown inconsistent blood circulation half-life according to the modified methods, and t...

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Published in:Theranostics 2019-01, Vol.9 (12), p.3398-3409
Main Authors: Park, Ji Yong, Song, Myung Geun, Kim, Woo Hyoung, Kim, Kyu Wan, Lodhi, Nadeem Ahmed, Choi, Jin Yeong, Kim, Young Ju, Kim, Jung Young, Chung, Hyewon, Oh, Chiwoo, Lee, Yun-Sang, Kang, Keon Wook, Im, Hyung-Jun, Seok, Seung Hyeok, Lee, Dong Soo, Kim, Edmund E, Jeong, Jae Min
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Language:English
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Research Paper
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Summary:Albumin is one of the most attractive nanoplatforms for targeted imaging and drug delivery due to its biocompatibility and long circulation half-life. However, previously reported albumin-based nanoplatforms have shown inconsistent blood circulation half-life according to the modified methods, and the affecting factors were not well evaluated, which could hamper the clinical translation of albumin-based nanoplatforms. Herein, we developed a finely tuned click-chemistry based albumin nanoplatform (CAN) with a longer circulation half-life and an efficient tumor targeting ability. CAN was synthesized in two steps. First, albumin was conjugated with ADIBO-NHS (albumin-ADIBO) by reacting albumin with various molar ratios of ADIBO. The number of attached ADIBO moieties was determined using matrix-assisted laser desorption ionization time of flight (MALDI-TOF). Second, the desired modalities including azide-functionalized chelator, a fluorescence dye, and folate were incorporated into albumin-ADIBO using strain-promoted alkyne-azide cycloaddition reaction (SPAAC reaction). The biodistribution and targeting efficiency of functionalized CANs were demonstrated in mice. The degree of functionalization (DOF) and resulting biodistribution was controlled precisely using the click chemistry approach. Specifically, the numbers of attached azadibenzocyclooctyne (ADIBO) moieties on albumin, the DOF, were optimized by reacting albumin with varying molar ratios of ADIBO with a high reproducibility. Furthermore, we developed a simple and efficient method to estimate the DOF using - spectrophotometry (UV-vis), which was further validated by matrix-assisted laser desorption ionization time of flight (MALDI-TOF). The biodistribution of CAN could be controlled by DOF, and CAN with an optimized DOF showed a long circulation half-life (> 18 h). CAN was further functionalized using a simple click chemistry reaction with an azide functionalized chelator, a fluorescence dye, and folate. Cu- and folate-labeled CAN ( Cu-CAN-FA) showed effective and specific folate receptor targeting , with an over two-fold higher uptake than the liver at 24 h post-injection. Our development from the precisely controlled DOF demonstrates that an optimized CAN can be used as a multifunctional nanoplatform to obtain a longer half-life with radioisotopes and ligands, and provides an effective method for the development of albumin-based tumor theranostic agents.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.33143