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ACS Nano. 2017 Oct 24;11(10):10147-10158. doi: 10.1021/acsnano.7b04736. Epub 2017 Sep 18.

Inhibiting Metastasis and Preventing Tumor Relapse by Triggering Host Immunity with Tumor-Targeted Photodynamic Therapy Using Photosensitizer-Loaded Functional Nanographenes.

Author information

1
Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center , Beijing 100191, China.
2
Medical and Healthy Analytical Center, Peking University , Beijing 100191, China.
3
Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101, China.
4
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.

Abstract

Effective cancer therapy depends not only on destroying the primary tumor but also on conditioning the host immune system to recognize and eliminate residual tumor cells and prevent metastasis. In this study, a tumor integrin αvβ6-targeting peptide (the HK peptide)-functionalized graphene oxide (GO) was coated with a photosensitizer (HPPH). The resulting GO conjugate, GO(HPPH)-PEG-HK, was investigated whether it could destroy primary tumors and boost host antitumor immunity. We found that GO(HPPH)-PEG-HK exhibited significantly higher tumor uptake than GO(HPPH)-PEG and HPPH. Photodynamic therapy (PDT) using GO(HPPH)-PEG suppressed tumor growth in both subcutaneous and lung metastatic mouse models. Necrotic tumor cells caused by GO(HPPH)-PEG-HK PDT activated dendritic cells and significantly prevented tumor growth and lung metastasis by increasing the infiltration of cytotoxic CD8+ T lymphocytes within tumors as evidenced by in vivo optical and single-photon emission computed tomography (SPECT)/CT imaging. These results demonstrate that tumor-targeted PDT using GO(HPPH)-PEG-HK could effectively ablate primary tumors and destroy residual tumor cells, thereby preventing distant metastasis by activating host antitumor immunity and suppressing tumor relapse by stimulation of immunological memory.

KEYWORDS:

graphene oxide; immunological memory; immunotherapy; photodynamic therapy; tumor vaccine

PMID:
28901740
DOI:
10.1021/acsnano.7b04736
[Indexed for MEDLINE]

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