Sulfonated Amphiphilic Poly(α)glutamate Amine-A Potential siRNA Nanocarrier for the Treatment of Both Chemo-Sensitive and Chemo-Resistant Glioblastoma Tumors
Development of chemo-resistance is a major challenge in glioblastoma (GB) treatment. This phenomenon is often driven by increased activation of genes associated with DNA repair, such as the alkyl-removing enzyme O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) in combination with...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Book |
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MDPI AG,
2021-12-01T00:00:00Z.
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| 001 | doaj_ad9519e41bd14d16b70db74e4d6f2122 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Adva Krivitsky |e author |
| 700 | 1 | 0 | |a Sabina Pozzi |e author |
| 700 | 1 | 0 | |a Eilam Yeini |e author |
| 700 | 1 | 0 | |a Sahar Israeli Dangoor |e author |
| 700 | 1 | 0 | |a Tal Zur |e author |
| 700 | 1 | 0 | |a Sapir Golan |e author |
| 700 | 1 | 0 | |a Vadim Krivitsky |e author |
| 700 | 1 | 0 | |a Nitzan Albeck |e author |
| 700 | 1 | 0 | |a Evgeny Pisarevsky |e author |
| 700 | 1 | 0 | |a Paula Ofek |e author |
| 700 | 1 | 0 | |a Asaf Madi |e author |
| 700 | 1 | 0 | |a Ronit Satchi-Fainaro |e author |
| 245 | 0 | 0 | |a Sulfonated Amphiphilic Poly(α)glutamate Amine-A Potential siRNA Nanocarrier for the Treatment of Both Chemo-Sensitive and Chemo-Resistant Glioblastoma Tumors |
| 260 | |b MDPI AG, |c 2021-12-01T00:00:00Z. | ||
| 500 | |a 10.3390/pharmaceutics13122199 | ||
| 500 | |a 1999-4923 | ||
| 520 | |a Development of chemo-resistance is a major challenge in glioblastoma (GB) treatment. This phenomenon is often driven by increased activation of genes associated with DNA repair, such as the alkyl-removing enzyme O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) in combination with overexpression of canonical genes related to cell proliferation and tumor progression, such as Polo-like kinase 1 (Plk1). Hereby, we attempt to sensitize resistant GB cells using our established amphiphilic poly(α)glutamate (APA): small interfering RNA (siRNA) polyplexes, targeting Plk1. Furthermore, we improved brain-targeting by decorating our nanocarrier with sulfonate groups. Our sulfonated nanocarrier showed superior selectivity towards P-selectin (SELP), a transmembrane glycoprotein overexpressed in GB and angiogenic brain endothelial cells. Self-assembled polyplexes of sulfonated APA and siPlk1 internalized into GB cells and into our unique 3-dimensional (3D) GB spheroids inducing specific gene silencing. Moreover, our RNAi nanotherapy efficiently reduced the cell viability of both chemo-sensitive and chemo-resistant GB cells. Our developed sulfonated amphiphilic poly(α)glutamate nanocarrier has the potential to target siRNA to GB brain tumors. Our findings may strengthen the therapeutic applications of siRNA for chemo-resistant GB tumors, or as a combination therapy for chemo-sensitive GB tumors. | ||
| 546 | |a EN | ||
| 690 | |a nanocarrier | ||
| 690 | |a polyplexes | ||
| 690 | |a siRNA delivery | ||
| 690 | |a glioblastoma therapy | ||
| 690 | |a amphiphilic poly(α)glutamate | ||
| 690 | |a P-selectin | ||
| 690 | |a Pharmacy and materia medica | ||
| 690 | |a RS1-441 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Pharmaceutics, Vol 13, Iss 12, p 2199 (2021) | |
| 787 | 0 | |n https://www.mdpi.com/1999-4923/13/12/2199 | |
| 787 | 0 | |n https://doaj.org/toc/1999-4923 | |
| 856 | 4 | 1 | |u https://doaj.org/article/ad9519e41bd14d16b70db74e4d6f2122 |z Connect to this object online. |