Multistage signal-interactive nanoparticles improve tumor targeting through efficient nanoparticle-cell communications
Cell Reports, vol. 35, pp. 109131
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.
Authors 15
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University of Helsinki · Shanghai Jiao Tong University · Ruijin Hospital
Affiliation as printed
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
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
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland
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Northwestern Polytechnical University · Shanghai Jiao Tong University · Ruijin Hospital
Affiliation as printed
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
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
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Li Kong Aachen
Leiden University · Huazhong University of Science and Technology
Affiliation as printed
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
Leiden Institute of Chemistry, Leiden University, P.O. Box 9052, 2300 RA Leiden, the Netherlands
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, P.R. China
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Shanghai Jiao Tong University · Ruijin Hospital
Affiliation as printed
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
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Northwestern Polytechnical University · Shanghai Jiao Tong University · Ruijin Hospital
Affiliation as printed
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
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
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Affiliation as printed
Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, 20014 Turku, Finland
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Affiliation as printed
Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, 20014 Turku, Finland
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Affiliation as printed
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland
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Shanghai Jiao Tong University · Shanghai Sixth People's Hospital
Affiliation as printed
Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai 200233, P.R. China
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Shanghai Jiao Tong University · Shanghai Sixth People's Hospital
Affiliation as printed
Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai 200233, P.R. China
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Shanghai Jiao Tong University · Ruijin Hospital
Affiliation as printed
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
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Hongbo Zhang corresponding
Åbo Akademi University · University of Turku · Shanghai Jiao Tong University · Ruijin Hospital
Affiliation as printed
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
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
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Alexander Kros Aachen
Affiliation as printed
Leiden Institute of Chemistry, Leiden University, P.O. Box 9052, 2300 RA Leiden, the Netherlands
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Wenguo Cui corresponding
Shanghai Jiao Tong University · Ruijin Hospital
Affiliation as printed
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
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
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Hélder A. Santos corresponding
University of Helsinki · HiLIFE – Elämäntieteiden Instituutti
Affiliation as printed
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
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
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