Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA
Abstract Background To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA...
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-020-00758-4 |
| _version_ | 1828392935101562880 |
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| author | Long Zhang Chaofeng Mu Tinghong Zhang Dejun Yang Chenou Wang Qiong Chen Lin Tang Luhui Fan Cong Liu Jianliang Shen Huaqiong Li |
| author_facet | Long Zhang Chaofeng Mu Tinghong Zhang Dejun Yang Chenou Wang Qiong Chen Lin Tang Luhui Fan Cong Liu Jianliang Shen Huaqiong Li |
| author_sort | Long Zhang |
| collection | DOAJ |
| description | Abstract Background To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery. Results Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo. Conclusions The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy. |
| first_indexed | 2024-12-10T07:30:09Z |
| format | Article |
| id | doaj.art-e176d2a889124dc8b32caca3ba455aa2 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-12-10T07:30:09Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-e176d2a889124dc8b32caca3ba455aa22022-12-22T01:57:36ZengBMCJournal of Nanobiotechnology1477-31552021-01-0119111210.1186/s12951-020-00758-4Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNALong Zhang0Chaofeng Mu1Tinghong Zhang2Dejun Yang3Chenou Wang4Qiong Chen5Lin Tang6Luhui Fan7Cong Liu8Jianliang Shen9Huaqiong Li10School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversityDepartment of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang Chinese Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversityDepartment of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang Chinese Medical UniversityDepartment of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang Chinese Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversitySchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical UniversityAbstract Background To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery. Results Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo. Conclusions The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.https://doi.org/10.1186/s12951-020-00758-4RNA nanoparticlesXBP1siRNATNBCChemoresistance |
| spellingShingle | Long Zhang Chaofeng Mu Tinghong Zhang Dejun Yang Chenou Wang Qiong Chen Lin Tang Luhui Fan Cong Liu Jianliang Shen Huaqiong Li Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA Journal of Nanobiotechnology RNA nanoparticles XBP1 siRNA TNBC Chemoresistance |
| title | Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA |
| title_full | Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA |
| title_fullStr | Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA |
| title_full_unstemmed | Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA |
| title_short | Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA |
| title_sort | development of targeted therapy therapeutics to sensitize triple negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging rna |
| topic | RNA nanoparticles XBP1 siRNA TNBC Chemoresistance |
| url | https://doi.org/10.1186/s12951-020-00758-4 |
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