Multistage signal-interactive nanoparticles improve tumor targeting through efficient nanoparticle-cell communications

Feng Zhang; Yiran Zhang; Li Kong; Huanhuan Luo; Yuezhou Zhang; Ermei Mäkilä; Jarno Salonen; Jouni T Hirvonen; Yueqi Zhu; Yingsheng Cheng; Lianfu Deng; Hongbo Zhang; Alexander Kros; Wenguo Cui; Hélder A Santos

doi:10.1016/j.celrep.2021.109131

Multistage signal-interactive nanoparticles improve tumor targeting through efficient nanoparticle-cell communications

Cell Rep. 2021 May 25;35(8):109131. doi: 10.1016/j.celrep.2021.109131.

Authors

Feng Zhang¹, Yiran Zhang², Li Kong³, Huanhuan Luo², Yuezhou Zhang⁴, Ermei Mäkilä⁵, Jarno Salonen⁵, Jouni T Hirvonen⁶, Yueqi Zhu⁷, Yingsheng Cheng⁷, Lianfu Deng², Hongbo Zhang⁸, Alexander Kros⁹, Wenguo Cui¹⁰, Hélder A Santos¹¹

Affiliations

¹ Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland; Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P.R. China.
² Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P.R. China.
³ Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, P.R. China; Leiden Institute of Chemistry, Leiden University, P.O. Box 9052, 2300 RA Leiden, the Netherlands.
⁴ Xían Institute of Flexible Electronics & Xían Institute of Biomedical Materials and Engineering, Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xían 710072, P.R. China.
⁵ Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, 20014 Turku, Finland.
⁶ Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland.
⁷ Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai 200233, P.R. China.
⁸ Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P.R. China; Pharmaceutical Sciences Laboratory, Åbo Akademi University; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku 20520, Finland. Electronic address: hongbo.zhang@abo.fi.
⁹ Leiden Institute of Chemistry, Leiden University, P.O. Box 9052, 2300 RA Leiden, the Netherlands.
¹⁰ Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P.R. China. Electronic address: wgcui80@hotmail.com.
¹¹ Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland; Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00014 Helsinki, Finland. Electronic address: helder.santos@helsinki.fi.

Abstract

Communication between biological components is critical for homeostasis maintenance among the convergence of complicated bio-signals. For therapeutic nanoparticles (NPs), the general lack of effective communication mechanisms with the external cellular environment causes loss of homeostasis, resulting in deprived autonomy, severe macrophage-mediated clearance, and limited tumor accumulation. Here, we develop a multistage signal-interactive system on porous silicon particles through integrating the Self-peptide and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide into a hierarchical chimeric signaling interface with "don't eat me" and "eat me" signals. This biochemical transceiver can act as both the signal receiver for amantadine to achieve NP transformation and signal conversion as well as the signal source to present different signals sequentially by reversible self-mimicking. Compared with the non-interactive controls, these signal-interactive NPs loaded with AS1411 and tanespimycin (17-AAG) as anticancer drugs improve tumor targeting 2.8-fold and tumor suppression 6.5-fold and showed only 51% accumulation in the liver with restricted hepatic injury.

Keywords: multistage signal interaction; nanoparticle-cell communication; reversible self-mimicking; tumor targeting.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Communication / immunology*
Humans
Models, Molecular
Nanoparticles / metabolism*
Neoplasm Staging
Neoplasms / immunology*
Signal Transduction