用等离子体金纳米星标记的人脂肪来源干细胞用于细胞追踪和光热消融癌细胞
Human Adipose-Derived Stem Cells Labeled with Plasmonic Gold Nanostars for Cellular Tracking and Photothermal Cancer Cell Ablation.
作者信息
Shammas Ronnie L, Fales Andrew M, Crawford Bridget M, Wisdom Amy J, Devi Gayathri R, Brown David A, Vo-Dinh Tuan, Hollenbeck Scott T
机构信息
Durham, N.C.
From Duke University School of Medicine, the Departments of Biomedical Engineering and Chemistry and the Fitzpatrick Institute for Photonics, Duke University, the Department of Surgery, Duke University Medical Center, and the Division of Plastic, Maxillofacial and Oral Surgery; Duke University Health System.
出版信息
Plast Reconstr Surg. 2017 Apr;139(4):900e-910e. doi: 10.1097/PRS.0000000000003187.
BACKGROUND
Gold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches in response to chemokines. The ability of adipose-derived stem cells to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics.
METHODS
To test the labeling efficiency of gold nanostars, undifferentiated adipose-derived stem cells were incubated with gold nanostars and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence microscopy. The effects of gold nanostars on cell phenotype, proliferation, and viability were assessed with flow cytometry, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide metabolic assay, and trypan blue, respectively. Trilineage differentiation of gold nanostar-labeled adipose-derived stem cells was induced with the appropriate media. Photothermolysis was performed on adipose-derived stem cells cultured alone or in co-culture with SKBR3 cancer cells.
RESULTS
Efficient uptake of gold nanostars occurred in adipose-derived stem cells, with persistence of the luminescent signal over 4 days. Labeling efficiency and signal quality were greater than with Qtracker. Gold nanostars did not affect cell phenotype, viability, or proliferation, and exhibited stronger luminescence than Qtracker throughout differentiation. Zones of complete ablation surrounding the gold nanostar-labeled adipose-derived stem cells were observed following photothermolysis in both monoculture and co-culture models.
CONCLUSIONS
Gold nanostars effectively label adipose-derived stem cells without altering cell phenotype. Once labeled, photoactivation of gold nanostar-labeled adipose-derived stem cells ablates neighboring cancer cells, demonstrating the potential of adipose-derived stem cells as a vehicle for the delivery of site-specific cancer therapy.
背景
金纳米星是独特的纳米平台,能够实时成像并将光能转化为热能以消融细胞。脂肪来源的干细胞会响应趋化因子向肿瘤微环境迁移。脂肪来源的干细胞迁移并整合到肿瘤中的能力使其成为癌症纳米治疗靶向递送的理想载体。
方法
为测试金纳米星的标记效率,将未分化的脂肪来源干细胞与金纳米星及一种市售纳米颗粒(Qtracker)一起孵育,然后使用双光子光致发光显微镜成像。分别通过流式细胞术、3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐代谢测定法和台盼蓝评估金纳米星对细胞表型、增殖和活力的影响。用适当的培养基诱导金纳米星标记的脂肪来源干细胞进行三系分化。对单独培养或与SKBR3癌细胞共培养的脂肪来源干细胞进行光热解。
结果
脂肪来源干细胞有效摄取金纳米星,发光信号持续4天以上。标记效率和信号质量高于Qtracker。金纳米星不影响细胞表型、活力或增殖,并且在整个分化过程中比Qtracker表现出更强的发光。在单培养和共培养模型中进行光热解后,观察到金纳米星标记的脂肪来源干细胞周围有完全消融的区域。
结论
金纳米星可有效标记脂肪来源干细胞而不改变细胞表型。一旦标记,金纳米星标记的脂肪来源干细胞的光激活会消融邻近癌细胞,证明脂肪来源干细胞作为递送位点特异性癌症治疗载体的潜力。