Multifunctional silver nanocluster-hybrid oligonucleotide vehicle for cell imaging and microRNA-targeted gene silencing.
Novel therapeutics is urgently needed to prevent cancer-related deaths. MicroRNAs that act as tumor suppressors have been recognized as a next-generation tumor therapy, and the restoration of tumor-suppressive microRNAs using microRNA replacements or mimics may be a less toxic, more effective strategy due to fewer off-target effects. Here, we designed the novel multifunctional oligonucleotide nanocarrier complex composed of a tumor-targeting aptamer sequence specific to mucin 1 (MUC1), poly-cytosine region for fluorescent silver nanocluster (AgNC) synthesis, and complimentary sequence for microRNA miR-34a loading. MiR-34a was employed because of its therapeutic effect of inhibiting oncogene expression and inducing apoptosis in carcinomas. By monitoring the intrinsic fluorescence of AgNC, it was clearly shown that the constructed complex (MUC1-AgNCm-miR-34a) enters MCF-7 cells. To evaluate the efficacy of this nanocarrier for microRNA delivery, we investigated the gene and protein expression levels of downstream miR-34a targets (BCL-2, CDK6, and CCND1) by quantitative PCR and western blotting, respectively, and the results indicated their effective inhibition by miR-34a. This novel multifunctional AgNC-based nanocarrier can aid in improving the efficacy of breast cancer theranostics.
Department of Applied Chemistry, National Chiao-Tung University, No. 1001 Ta-Hsueh Road, Hsinchu 30010, Taiwan.
Hau-Yun
HY
Chen
Institute of Molecular Science, National Chiao-Tung University, No. 1001 Ta-Hsueh Road, Hsinchu 30010, Taiwan.
Karunya
K
Albert
Department of Applied Chemistry, National Chiao-Tung University, No. 1001 Ta-Hsueh Road, Hsinchu 30010, Taiwan.
Cheng-Che
CC
Wen
Department of Applied Chemistry, National Chiao-Tung University, No. 1001 Ta-Hsueh Road, Hsinchu 30010, Taiwan.
Pei-Ying
PY
Hsieh
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan.
Sih-Yu
SY
Chen
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan.
Nei-Chung
NC
Huang
Material and Chemical Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
Shen-Chuan
SC
Lo
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan.
Jen-Kun
JK
Chen
Department of Applied Chemistry, National Chiao-Tung University, No. 1001 Ta-Hsueh Road, Hsinchu 30010, Taiwan; Institute of Molecular Science, National Chiao-Tung University, No. 1001 Ta-Hsueh Road, Hsinchu 30010, Taiwan. Electronic address: hyhsu99@nctu.edu.tw.
Hsin-Yun
HY
Hsu
D052157:Aptamers, Nucleotide / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000502:physiology; D018014:Gene Transfer Techniques; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000008:administration & dosage / Q000737:chemistry; D018396:Mucin-1 / Q000235:genetics; D053758:Nanoparticles / Q000737:chemistry*; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry*; D012834:Silver / Q000737:chemistry*
D052157:Aptamers, Nucleotide; C522425:MIRN34 microRNA, human; C060192:MUC1 protein, human; D035683:MicroRNAs; D018396:Mucin-1; D009841:Oligonucleotides; D012834:Silver
Cancer theranostics; Human breast adenocarcinoma; RNAi; Silver nanocluster; microRNA