Department of Electrical, Computer, and Energy Engineering, University of Colorado, Boulder, CO 80309, USA.
Division of Medical Oncology, School of Medicine, University of Colorado Denver, 12801 E. 17(th) Ave. Aurora, CO 80045, USA.
Mater Sci Eng C Mater Biol Appl. 2019 Apr;97:784-792. doi: 10.1016/j.msec.2018.12.113. Epub 2018 Dec 29.
This paper reports successful synthesis of multifunctional nanoclusters of upconversion nanoparticle (UCNP) and gold nanorod (AuNR) through a PEGylation process. UCNPs emit visible luminescence under near-infrared excitation, producing high-contrast images with no background fluorescence. When coupled with AuNRs, the resulting UCNP-AuNR multifunctional nanoclusters are capable of simultaneous detection and treatment of bladder cancer. These UCNP-AuNR nanoclusters are further functionalized with antibodies to epidermal growth factor receptor (EGFR) to target bladder cancer cells known to overexpress EGFRs. This paper demonstrates, for the first time, efficient targeting of bladder cancer cells with UCNP-AuNR nanoclusters. In addition to high-contrast imaging and consequently high sensitivity detection of bladder cancer cells, highly selective optoporation-assisted chemotherapy was accomplished using a dosage of chemotherapy agent significantly lower than any previous reports, within a clinically relevant incubation time window. These results are highly relevant to the eventual human application in which the nanoclusters and chemotherapy drugs will be directly instilled in bladder via urinary catheter.
本文通过聚乙二醇(PEGylation)过程成功合成了上转换纳米粒子(UCNP)和金纳米棒(AuNR)的多功能纳米簇。UCNP 在近红外激发下发出可见光荧光,产生无背景荧光的高对比度图像。当与 AuNR 结合时,所得到的 UCNP-AuNR 多功能纳米簇能够同时检测和治疗膀胱癌。这些 UCNP-AuNR 纳米簇进一步用针对表皮生长因子受体(EGFR)的抗体功能化,以靶向已知过表达 EGFR 的膀胱癌细胞。本文首次证明了 UCNP-AuNR 纳米簇对膀胱癌细胞的高效靶向。除了对膀胱癌细胞进行高对比度成像和因此具有高灵敏度检测外,还使用明显低于以往任何报告的化疗药物剂量,在临床相关的孵育时间窗口内完成了高度选择性的光孔辅助化学疗法。这些结果与最终的人体应用高度相关,其中纳米簇和化疗药物将通过导尿管直接注入膀胱。