Cargando…
PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer
OBJECTIVE: This study aimed to develop aptamer-anchored hyperbranched poly(amido amine) (HPAA) for the systemic delivery of miRNA-133a-3p and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro. METHODS: A glutathione (GSH)-responsive cationic HPAA w...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533908/ https://www.ncbi.nlm.nih.gov/pubmed/33061374 http://dx.doi.org/10.2147/IJN.S268398 |
_version_ | 1783590216614805504 |
---|---|
author | Ye, Yongheng Zhang, Lingli Dai, Yuhu Wang, Zhi Li, Cuie Peng, Yue Ma, Dong He, Peiheng |
author_facet | Ye, Yongheng Zhang, Lingli Dai, Yuhu Wang, Zhi Li, Cuie Peng, Yue Ma, Dong He, Peiheng |
author_sort | Ye, Yongheng |
collection | PubMed |
description | OBJECTIVE: This study aimed to develop aptamer-anchored hyperbranched poly(amido amine) (HPAA) for the systemic delivery of miRNA-133a-3p and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro. METHODS: A glutathione (GSH)-responsive cationic HPAA was prepared by the Michael addition reaction. Furthermore, HPAA-PEG was produced by PEGylation, and then the aptamer targeted to prostate-specific membrane antigen (PSMA) was conjugated to the HPAA-PEG. The obtained HPAA-PEG-APT could form nanocomplexes with miRNA-133a-3p through electrostatic adsorption. RESULTS: The results of immunocytochemistry indicated that the complexes could target PSMA-expressing LNCaP cells. The ability of HPAA-PEG-APT to facilitate the delivery of miRNA-133a-3p into LNCaP cells was proven, and HPAA-PEG-APT/miRNA-133a-3p demonstrated enhanced antitumor activity, lower cytotoxicity and better biocompatibility in vitro. Moreover, in a mouse tibial injection tumor model, the intravenous injection of the HPAA-PEG-APT/miRNA-133a-3p complex significantly inhibited cancer growth and extended the survival time. CONCLUSION: This study provided an aptamer-anchored HPAA-loaded gene system to deliver miRNA-133a-3p for better therapeutic efficacy of bone metastasis of prostate cancer. |
format | Online Article Text |
id | pubmed-7533908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-75339082020-10-14 PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer Ye, Yongheng Zhang, Lingli Dai, Yuhu Wang, Zhi Li, Cuie Peng, Yue Ma, Dong He, Peiheng Int J Nanomedicine Original Research OBJECTIVE: This study aimed to develop aptamer-anchored hyperbranched poly(amido amine) (HPAA) for the systemic delivery of miRNA-133a-3p and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro. METHODS: A glutathione (GSH)-responsive cationic HPAA was prepared by the Michael addition reaction. Furthermore, HPAA-PEG was produced by PEGylation, and then the aptamer targeted to prostate-specific membrane antigen (PSMA) was conjugated to the HPAA-PEG. The obtained HPAA-PEG-APT could form nanocomplexes with miRNA-133a-3p through electrostatic adsorption. RESULTS: The results of immunocytochemistry indicated that the complexes could target PSMA-expressing LNCaP cells. The ability of HPAA-PEG-APT to facilitate the delivery of miRNA-133a-3p into LNCaP cells was proven, and HPAA-PEG-APT/miRNA-133a-3p demonstrated enhanced antitumor activity, lower cytotoxicity and better biocompatibility in vitro. Moreover, in a mouse tibial injection tumor model, the intravenous injection of the HPAA-PEG-APT/miRNA-133a-3p complex significantly inhibited cancer growth and extended the survival time. CONCLUSION: This study provided an aptamer-anchored HPAA-loaded gene system to deliver miRNA-133a-3p for better therapeutic efficacy of bone metastasis of prostate cancer. Dove 2020-09-28 /pmc/articles/PMC7533908/ /pubmed/33061374 http://dx.doi.org/10.2147/IJN.S268398 Text en © 2020 Ye et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Ye, Yongheng Zhang, Lingli Dai, Yuhu Wang, Zhi Li, Cuie Peng, Yue Ma, Dong He, Peiheng PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer |
title | PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer |
title_full | PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer |
title_fullStr | PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer |
title_full_unstemmed | PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer |
title_short | PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer |
title_sort | psma-targeting reduction-cleavable hyperbranched polyamide-amine gene delivery system to treat the bone metastases of prostate cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533908/ https://www.ncbi.nlm.nih.gov/pubmed/33061374 http://dx.doi.org/10.2147/IJN.S268398 |
work_keys_str_mv | AT yeyongheng psmatargetingreductioncleavablehyperbranchedpolyamideaminegenedeliverysystemtotreatthebonemetastasesofprostatecancer AT zhanglingli psmatargetingreductioncleavablehyperbranchedpolyamideaminegenedeliverysystemtotreatthebonemetastasesofprostatecancer AT daiyuhu psmatargetingreductioncleavablehyperbranchedpolyamideaminegenedeliverysystemtotreatthebonemetastasesofprostatecancer AT wangzhi psmatargetingreductioncleavablehyperbranchedpolyamideaminegenedeliverysystemtotreatthebonemetastasesofprostatecancer AT licuie psmatargetingreductioncleavablehyperbranchedpolyamideaminegenedeliverysystemtotreatthebonemetastasesofprostatecancer AT pengyue psmatargetingreductioncleavablehyperbranchedpolyamideaminegenedeliverysystemtotreatthebonemetastasesofprostatecancer AT madong psmatargetingreductioncleavablehyperbranchedpolyamideaminegenedeliverysystemtotreatthebonemetastasesofprostatecancer AT hepeiheng psmatargetingreductioncleavablehyperbranchedpolyamideaminegenedeliverysystemtotreatthebonemetastasesofprostatecancer |