Research Article

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2018, 11(4): 2159–2172

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https://doi.org/10.1007/s12274-017-1833-7

Chemokine-mimetic plerixafor derivative for tumorspecific delivery of nanomaterials

Seungbeom Ko§, Gayong Shim§, Jinyoung Kim, and Yu-Kyoung Oh (*)

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College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Kwanak-ro, Kwanak-gu, Seoul 08826, Republic of Korea
§ Seungbeom Ko and Gayong Shim contributed equally to this work.

Keywords: chemokine-mimetic, plerixafor derivatives, chemokine receptor, nanomaterial, photothermal therapy
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ABSTRACT Here, we report that chemokine-mimetic plerixafor derivatives could govern tumor-specific delivery and functional effects of nanomaterials. Reduced graphene oxide (rGO) nanosheets were used as a model functional nanomaterial, and plerixafor-conjugated lipid (PL/rGO) or a benzylcyclam derivative of plerixaforconjugated lipid (BPL/rGO) was physically adsorbed onto the surface of rGO. The cellular uptake of surface-modified rGO was dependent on overexpression of the CXCR4 chemokine receptor on cancer cells. In KB cells, the binding affinity of BPL/rGO for CXCR4 was 6.8-fold greater than that of PL/rGO. Notably, cellular uptake patterns correlated with in vitro photothermal anticancer efficacy. The tumor distribution of BPL/rGO was higher than that of PL/rGO and plain rGO in mice bearing CXCR4-overexpressing tumors, whereas the distribution of the various rGO forms was similar in mice harboring CXCR4-negative tumors. Moreover, complete photothermal tumor ablation was observed in BPL/rGOtreated mice bearing CXCR4-positive KB cell tumors, but not in CXCR4-negative MCF-7 cell tumors. These results provide evidence that BPL can be used to enhance the delivery of nanomaterials to CXCR4-overexpressing tumors. Chemokine-mimetic BPL can be further applied for nanomaterial-based delivery of photosensitizers, anticancer drugs, or diagnostic tumor imaging agents in CXCR4-overexpressing cancer patients.
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Chemokine-mimetic plerixafor derivative for tumorspecific delivery of nanomaterials. Nano Res. 2018, 11(4): 2159–2172 https://doi.org/10.1007/s12274-017-1833-7

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