Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer
Abstract Background Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly d...
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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/s12951-020-00756-6 |
| _version_ | 1828355134259724288 |
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| author | Yiran Zhang Yanming Wang Li Meng Qingqing Huang Yueqi Zhu Wenguo Cui Yingsheng Cheng Ranlu Liu |
| author_facet | Yiran Zhang Yanming Wang Li Meng Qingqing Huang Yueqi Zhu Wenguo Cui Yingsheng Cheng Ranlu Liu |
| author_sort | Yiran Zhang |
| collection | DOAJ |
| description | Abstract Background Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. Results The particle size of the micelles was 42 nm, the zeta potential increased from − 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. Conclusions This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs. |
| first_indexed | 2024-04-14T02:37:31Z |
| format | Article |
| id | doaj.art-1c039f49a0dc4b2aa8e77109e7535fbb |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T02:37:31Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-1c039f49a0dc4b2aa8e77109e7535fbb2022-12-22T02:17:19ZengBMCJournal of Nanobiotechnology1477-31552021-01-0119111510.1186/s12951-020-00756-6Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancerYiran Zhang0Yanming Wang1Li Meng2Qingqing Huang3Yueqi Zhu4Wenguo Cui5Yingsheng Cheng6Ranlu Liu7Tianjin Institute of Urology & Department of Urology, The Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Molecular Drug Research, College of Pharmacy, Nankai University College of Pharmacy, Nankai UniversityTianjin Key Laboratory of Molecular Drug Research, College of Pharmacy, Nankai University College of Pharmacy, Nankai UniversityTianjin Key Laboratory of Molecular Drug Research, College of Pharmacy, Nankai University College of Pharmacy, Nankai UniversityDepartment of Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalTianjin Institute of Urology & Department of Urology, The Second Hospital of Tianjin Medical UniversityAbstract Background Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. Results The particle size of the micelles was 42 nm, the zeta potential increased from − 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. Conclusions This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.https://doi.org/10.1186/s12951-020-00756-6MicellesTargeted ligandEPRProstate cancerGene therapy |
| spellingShingle | Yiran Zhang Yanming Wang Li Meng Qingqing Huang Yueqi Zhu Wenguo Cui Yingsheng Cheng Ranlu Liu Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer Journal of Nanobiotechnology Micelles Targeted ligand EPR Prostate cancer Gene therapy |
| title | Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer |
| title_full | Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer |
| title_fullStr | Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer |
| title_full_unstemmed | Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer |
| title_short | Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer |
| title_sort | targeted micelles with chemotherapeutics and gene drugs to inhibit the g1 s and g2 m mitotic cycle of prostate cancer |
| topic | Micelles Targeted ligand EPR Prostate cancer Gene therapy |
| url | https://doi.org/10.1186/s12951-020-00756-6 |
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