Chemokine-mimetic plerixafor derivative for tumorspecific delivery of nanomaterials  

作　　者：Seungbeom Ko Gayong Shim Jinyoung Kim Yu-Kyoung Oh 

机构地区：[1]College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Kwanak-ro, Kwanak-gu, Seoul 08826, Republic of Korea

出　　处：《Nano Research》2018年第4期2159-2172,共14页纳米研究（英文版）

摘　　要：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 plerixafor- conjugated 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/rGO- treated 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.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 plerixafor- conjugated 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/rGO- treated 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.

关 键 词：chemokine-mimetic plerixafor derivatives chemokine receptor NANOMATERIAL photothermal therapy 

分 类 号：Q26[生物学—细胞生物学] TG142[一般工业技术—材料科学与工程]