Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts
Nucleic acid medicines have been developed as new therapeutic agents against various diseases; however, targeted delivery of these reagents into cancer cells, particularly hematologic cancer cells, via systemic administration is limited by the lack of efficient and cell-specific delivery systems. We...
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MDPI AG
2022-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/3/566 |
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| author | Emi Soma Asako Yamayoshi Yuki Toda Yuji Mishima Shigekuni Hosogi Eishi Ashihara |
| author_facet | Emi Soma Asako Yamayoshi Yuki Toda Yuji Mishima Shigekuni Hosogi Eishi Ashihara |
| author_sort | Emi Soma |
| collection | DOAJ |
| description | Nucleic acid medicines have been developed as new therapeutic agents against various diseases; however, targeted delivery of these reagents into cancer cells, particularly hematologic cancer cells, via systemic administration is limited by the lack of efficient and cell-specific delivery systems. We previously demonstrated that monoclonal antibody (mAb)-oligonucleotide complexes targeting exosomal microRNAs with linear oligo-D-arginine (Arg) linkers were transferred into solid cancer cells and inhibited exosomal miRNA functions. In this study, we developed exosome-capturing anti-CD63 mAb-conjugated small interfering RNAs (siRNAs) with branched Arg linkers and investigated their effects on multiple myeloma (MM) cells. Anti-CD63 mAb-conjugated siRNAs were successfully incorporated into MM cells. The incorporation of exosomes was inhibited by endocytosis inhibitors. We also conducted a functional analysis of anti-CD63 mAb-conjugated siRNAs. Ab-conjugated <i>luciferase+</i> (<i>luc+</i>) siRNAs significantly decreased the luminescence intensity in OPM-2-luc+ cells. Moreover, treatment with anti-CD63 mAb-conjugated with <i>MYC</i> and <i>CTNNB1</i> siRNAs decreased the mRNA transcript levels of <i>MYC</i> and <i>CTNNB1</i> to 52.5% and 55.3%, respectively, in OPM-2 cells. In conclusion, exosome-capturing Ab-conjugated siRNAs with branched Arg linkers can be effectively delivered into MM cells via uptake of exosomes by parental cells. This technology has the potential to lead to a breakthrough in drug delivery systems for hematologic cancers. |
| first_indexed | 2024-03-10T00:07:56Z |
| format | Article |
| id | doaj.art-32e640e630944f2788d7da24c04f6e73 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:07:56Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-32e640e630944f2788d7da24c04f6e732023-11-23T16:04:59ZengMDPI AGCancers2072-66942022-01-0114356610.3390/cancers14030566Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA TranscriptsEmi Soma0Asako Yamayoshi1Yuki Toda2Yuji Mishima3Shigekuni Hosogi4Eishi Ashihara5Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, Kyoto 607-8414, JapanChemistry of Functional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, JapanDepartment of Clinical and Translational Physiology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, Kyoto 607-8414, JapanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USADepartment of Clinical and Translational Physiology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, Kyoto 607-8414, JapanDepartment of Clinical and Translational Physiology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, Kyoto 607-8414, JapanNucleic acid medicines have been developed as new therapeutic agents against various diseases; however, targeted delivery of these reagents into cancer cells, particularly hematologic cancer cells, via systemic administration is limited by the lack of efficient and cell-specific delivery systems. We previously demonstrated that monoclonal antibody (mAb)-oligonucleotide complexes targeting exosomal microRNAs with linear oligo-D-arginine (Arg) linkers were transferred into solid cancer cells and inhibited exosomal miRNA functions. In this study, we developed exosome-capturing anti-CD63 mAb-conjugated small interfering RNAs (siRNAs) with branched Arg linkers and investigated their effects on multiple myeloma (MM) cells. Anti-CD63 mAb-conjugated siRNAs were successfully incorporated into MM cells. The incorporation of exosomes was inhibited by endocytosis inhibitors. We also conducted a functional analysis of anti-CD63 mAb-conjugated siRNAs. Ab-conjugated <i>luciferase+</i> (<i>luc+</i>) siRNAs significantly decreased the luminescence intensity in OPM-2-luc+ cells. Moreover, treatment with anti-CD63 mAb-conjugated with <i>MYC</i> and <i>CTNNB1</i> siRNAs decreased the mRNA transcript levels of <i>MYC</i> and <i>CTNNB1</i> to 52.5% and 55.3%, respectively, in OPM-2 cells. In conclusion, exosome-capturing Ab-conjugated siRNAs with branched Arg linkers can be effectively delivered into MM cells via uptake of exosomes by parental cells. This technology has the potential to lead to a breakthrough in drug delivery systems for hematologic cancers.https://www.mdpi.com/2072-6694/14/3/566exosomeCD63siRNAnucleic acid medicinedrug delivery systemsantibody |
| spellingShingle | Emi Soma Asako Yamayoshi Yuki Toda Yuji Mishima Shigekuni Hosogi Eishi Ashihara Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts Cancers exosome CD63 siRNA nucleic acid medicine drug delivery systems antibody |
| title | Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts |
| title_full | Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts |
| title_fullStr | Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts |
| title_full_unstemmed | Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts |
| title_short | Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts |
| title_sort | successful incorporation of exosome capturing antibody sirna complexes into multiple myeloma cells and suppression of targeted mrna transcripts |
| topic | exosome CD63 siRNA nucleic acid medicine drug delivery systems antibody |
| url | https://www.mdpi.com/2072-6694/14/3/566 |
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