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J. Nanobiotechnol., Aug 19 2023, 21 (1) 279 | https://doi.org/10.1186/s12951-023-02057-0 Photosensitizing deep-seated cancer cells with photoprotein-conjugated upconversion nanoparticles.

Sung Hyun Park1†, Soohyun Han1†, Sangwoo Park2,3†, Hyung Shik Kim4, Kyung-Min Kim2, Suyeon Kim5, Dong Yun Lee4,6,7,8*, Joonseok Lee3,5,9* and Young-Pil Kim1,2,3,6,9,10*

1Department of HY-KIST Bio-Convergence, Hanyang University, Seoul 04763, Republic of Korea

2Department of Life Science, Hanyang University, Seoul 04763, Republic of Korea

3Research Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea

4Department of Bioengineering, College of Engineering, BK FOUR Biopharmaceutical Innovation Leader for Education and Research Group, Hanyang University, Seoul 04763, Republic of Korea

5Department of Chemistry, Hanyang University, Seoul 04763, Republic of Korea

6Institute of Nano Science and Technology, Hanyang University, Seoul 04763, Republic of Korea

7Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 04763, Republic of Korea

8Elixir Pharmatech Inc, Seoul 04763, Republic of Korea

9Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea

10Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Republic of Korea

†Sung Hyun Park, Soohyun Han and Sangwoo Park these authors contributed equally to this work.

*Correspondence: Dong Yun Lee, Joonseok Lee, Young-Pil Kim

Abstract

To resolve the problem of target specificity and light transmission to deep-seated tissues in photodynamic therapy (PDT), we report a cancer cell-targeted photosensitizer using photoprotein-conjugated upconversion nanoparticles (UCNPs) with high target specificity and efficient light transmission to deep tissues. Core-shell UCNPs with low internal energy back transfer were conjugated with recombinant proteins that consists of a photosensitizer (KillerRed; KR) and a cancer cell-targeted lead peptide (LP). Under near infrared (NIR)-irradiating condition, the UCNP-KR-LP generated superoxide anion radicals as reactive oxygen species via NIR-to-green light conversion and exhibited excellent specificity to target cancer cells through receptor-mediated cell adhesion. Consequently, this photosensitizing process facilitated rapid cell death in cancer cell lines (MCF-7, MDA-MB-231, and U-87MG) overexpressing integrin beta 1 (ITGB1) receptors but not in a cell line (SK-BR-3) with reduced ITGB1 expression and a non-invasive normal breast cell line (MCF-10A). In contrast to green light irradiation, NIR light irradiation exhibited significant PDT efficacy in cancer cells located beneath porcine skin tissues up to a depth of 10 mm, as well as in vivo tumor xenograft mouse models. This finding suggests that the designed nanocomposite is useful for sensing and targeting various deep-seated tumors.

논문정보

형식Research article
게재일2023년 08월 (BRIC 등록일 2023-09-07)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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