دورية أكاديمية
Harnessing Peptide-Functionalized Multivalent Gold Nanorods for Promoting Enhanced Gene Silencing and Managing Breast Cancer Metastasis.
| العنوان: | Harnessing Peptide-Functionalized Multivalent Gold Nanorods for Promoting Enhanced Gene Silencing and Managing Breast Cancer Metastasis. |
|---|---|
| المؤلفون: | Chakraborty K; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India., Biswas A; Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India., Mishra S; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India., Mallick AM; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India., Tripathi A; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India., Jan S; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India., Sinha Roy R; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India.; Centre for Advanced Functional Materials, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India.; Centre for Climate and Environmental Studies, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India. |
| المصدر: | ACS applied bio materials [ACS Appl Bio Mater] 2023 Feb 20; Vol. 6 (2), pp. 458-472. Date of Electronic Publication: 2023 Jan 18. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: ACS Publications Country of Publication: United States NLM ID: 101729147 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2576-6422 (Electronic) Linking ISSN: 25766422 NLM ISO Abbreviation: ACS Appl Bio Mater Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : ACS Publications, [2018]- |
| مواضيع طبية MeSH: | Metal Nanoparticles* , Nanotubes* , Neoplasms*, Animals ; Cell Line, Tumor ; Gene Silencing ; Gold ; RNA, Small Interfering/genetics ; RNA, Small Interfering/therapeutic use ; Zebrafish/genetics ; Humans ; Breast Neoplasms/pathology ; Xenograft Model Antitumor Assays ; Neoplasm Metastasis |
| مستخلص: | Small interfering RNA (siRNA) has become the cornerstone against undruggable targets and for managing metastatic breast cancer. However, an effective gene silencing approach is faced with a major challenge due to the delivery problem. In our present study, we have demonstrated efficient siRNA delivery, superior gene silencing, and inhibition of metastasis in triple-negative breast cancer cells (MDA-MB-231) using rod-shaped (aspect ratio: 4) multivalent peptide-functionalized gold nanoparticles and compared them to monovalent free peptide doses. Multivalency is a new concept in biology, and tuning the physical parameters of multivalent nanoparticles can enhance gene silencing and antitumor efficacy. We explored the effect of the multivalency of shape- and size-dependent peptide-functionalized gold nanoparticles in siRNA delivery. Our study demonstrates that peptide functionalization leads to reduced toxicity of the nanoparticles. Such designed peptide-functionalized nanorods also demonstrate antimetastatic efficacy in Notch1-silenced cells by preventing EMT progression in vitro . We have shown siRNA delivery in the hard-to-transfect primary cell line HUVEC and also demonstrated that the Notch1-silenced MDA-MB-231 cell line has failed to form nanobridge-mediated foci with the HUVEC in the co-culture of HUVEC and MDA-MB-231, which promote metastasis. This antimetastatic effect is further checked in a xenotransplant in vivo zebrafish model. In vivo studies also suggest that our designed nanoparticles mediated inhibition of micrometastasis due to silencing of the Notch1 gene. The outcome of our study highlights that the structure-activity relationship of multifunctional nanoparticles can be harnessed to modulate their biological activity. |
| فهرسة مساهمة: | Keywords: epithelial−mesenchymal transition; gold nanoparticle; metastasis; multivalency; peptide; siRNA; triple-negative breast cancer; zebrafish |
| المشرفين على المادة: | 7440-57-5 (Gold) 0 (RNA, Small Interfering) |
| تواريخ الأحداث: | Date Created: 20230118 Date Completed: 20230224 Latest Revision: 20230224 |
| رمز التحديث: | 20230224 |
| DOI: | 10.1021/acsabm.2c00726 |
| PMID: | 36651932 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 2576-6422 |
|---|---|
| DOI: | 10.1021/acsabm.2c00726 |