MUC1 aptamer-tethered H40-TEPA-PEG nanoconjugates for targeted siRNA-delivery and gene silencing in breast cancer cells
With a prevalence of 12.5% of all new cancer cases annually, breast cancer stands as the most common form of cancer worldwide. The current therapies utilized for breast cancer are constrained and ineffective in addressing the condition. siRNA-based gene silencing is a promising method for treating b...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2024.1383495/full |
| _version_ | 1797202060317294592 |
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| author | Rajesh Salve Rajesh Salve Niladri Haldar Niladri Haldar Aazam Shaikh Aazam Shaikh Rajkumar Samanta Rajkumar Samanta Devyani Sengar Devyani Sengar Surajit Patra Surajit Patra Virendra Gajbhiye Virendra Gajbhiye |
| author_facet | Rajesh Salve Rajesh Salve Niladri Haldar Niladri Haldar Aazam Shaikh Aazam Shaikh Rajkumar Samanta Rajkumar Samanta Devyani Sengar Devyani Sengar Surajit Patra Surajit Patra Virendra Gajbhiye Virendra Gajbhiye |
| author_sort | Rajesh Salve |
| collection | DOAJ |
| description | With a prevalence of 12.5% of all new cancer cases annually, breast cancer stands as the most common form of cancer worldwide. The current therapies utilized for breast cancer are constrained and ineffective in addressing the condition. siRNA-based gene silencing is a promising method for treating breast cancer. We have developed an aptamer-conjugated dendritic multilayered nanoconjugate to treat breast cancer. Initially, we transformed the hydroxyl groups of the hyperbranched bis-MPA polyester dendrimer into carboxylic groups. Subsequently, we linked these carboxylic groups to tetraethylenepentamine to form a positively charged dendrimer. In addition, the mucin-1 (MUC1) aptamer was attached to the dendrimer using a heterobifunctional polyethylene glycol. Characterizing dendrimers involved 1H NMR and dynamic light scattering techniques at every production stage. A gel retardation experiment was conducted to evaluate the successful binding of siRNA with targeted and non-targeted dendrimers. The targeted dendrimers exhibited no harmful effects on the NIH-3T3 fibroblast cells and RBCs, indicating their biocompatible characteristics. Confocal microscopy demonstrated significant higher uptake of targeted dendrimers than non-targeted dendrimers in MCF-7 breast cancer cells. The real-time PCR results demonstrated that the targeted dendrimers exhibited the most pronounced inhibition of the target gene expression compared to the non-targeted dendrimers and lipofectamine-2000. The caspase activation study confirmed the functional effect of survivin silencing by dendrimer, which led to the induction of apoptosis in breast cancer cells. The findings indicated that Mucin-1 targeted hyperbranched bis-MPA polyester dendrimer carrying siRNA could successfully suppress the expression of the target gene in breast cancer cells. |
| first_indexed | 2024-04-24T07:57:26Z |
| format | Article |
| id | doaj.art-a1f1f5e433d848d6a5233ab8d899344e |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-24T07:57:26Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-a1f1f5e433d848d6a5233ab8d899344e2024-04-18T05:02:17ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852024-04-011210.3389/fbioe.2024.13834951383495MUC1 aptamer-tethered H40-TEPA-PEG nanoconjugates for targeted siRNA-delivery and gene silencing in breast cancer cellsRajesh Salve0Rajesh Salve1Niladri Haldar2Niladri Haldar3Aazam Shaikh4Aazam Shaikh5Rajkumar Samanta6Rajkumar Samanta7Devyani Sengar8Devyani Sengar9Surajit Patra10Surajit Patra11Virendra Gajbhiye12Virendra Gajbhiye13Nanobioscience Group, Agharkar Research Institute, Pune, IndiaSavitribai Phule Pune University, Pune, IndiaNanobioscience Group, Agharkar Research Institute, Pune, IndiaSavitribai Phule Pune University, Pune, IndiaNanobioscience Group, Agharkar Research Institute, Pune, IndiaSavitribai Phule Pune University, Pune, IndiaNanobioscience Group, Agharkar Research Institute, Pune, IndiaSavitribai Phule Pune University, Pune, IndiaNanobioscience Group, Agharkar Research Institute, Pune, IndiaSavitribai Phule Pune University, Pune, IndiaNanobioscience Group, Agharkar Research Institute, Pune, IndiaSavitribai Phule Pune University, Pune, IndiaNanobioscience Group, Agharkar Research Institute, Pune, IndiaSavitribai Phule Pune University, Pune, IndiaWith a prevalence of 12.5% of all new cancer cases annually, breast cancer stands as the most common form of cancer worldwide. The current therapies utilized for breast cancer are constrained and ineffective in addressing the condition. siRNA-based gene silencing is a promising method for treating breast cancer. We have developed an aptamer-conjugated dendritic multilayered nanoconjugate to treat breast cancer. Initially, we transformed the hydroxyl groups of the hyperbranched bis-MPA polyester dendrimer into carboxylic groups. Subsequently, we linked these carboxylic groups to tetraethylenepentamine to form a positively charged dendrimer. In addition, the mucin-1 (MUC1) aptamer was attached to the dendrimer using a heterobifunctional polyethylene glycol. Characterizing dendrimers involved 1H NMR and dynamic light scattering techniques at every production stage. A gel retardation experiment was conducted to evaluate the successful binding of siRNA with targeted and non-targeted dendrimers. The targeted dendrimers exhibited no harmful effects on the NIH-3T3 fibroblast cells and RBCs, indicating their biocompatible characteristics. Confocal microscopy demonstrated significant higher uptake of targeted dendrimers than non-targeted dendrimers in MCF-7 breast cancer cells. The real-time PCR results demonstrated that the targeted dendrimers exhibited the most pronounced inhibition of the target gene expression compared to the non-targeted dendrimers and lipofectamine-2000. The caspase activation study confirmed the functional effect of survivin silencing by dendrimer, which led to the induction of apoptosis in breast cancer cells. The findings indicated that Mucin-1 targeted hyperbranched bis-MPA polyester dendrimer carrying siRNA could successfully suppress the expression of the target gene in breast cancer cells.https://www.frontiersin.org/articles/10.3389/fbioe.2024.1383495/fullmucin-1bis-MPA polyestersiRNAsurvivinbreast cancer |
| spellingShingle | Rajesh Salve Rajesh Salve Niladri Haldar Niladri Haldar Aazam Shaikh Aazam Shaikh Rajkumar Samanta Rajkumar Samanta Devyani Sengar Devyani Sengar Surajit Patra Surajit Patra Virendra Gajbhiye Virendra Gajbhiye MUC1 aptamer-tethered H40-TEPA-PEG nanoconjugates for targeted siRNA-delivery and gene silencing in breast cancer cells Frontiers in Bioengineering and Biotechnology mucin-1 bis-MPA polyester siRNA survivin breast cancer |
| title | MUC1 aptamer-tethered H40-TEPA-PEG nanoconjugates for targeted siRNA-delivery and gene silencing in breast cancer cells |
| title_full | MUC1 aptamer-tethered H40-TEPA-PEG nanoconjugates for targeted siRNA-delivery and gene silencing in breast cancer cells |
| title_fullStr | MUC1 aptamer-tethered H40-TEPA-PEG nanoconjugates for targeted siRNA-delivery and gene silencing in breast cancer cells |
| title_full_unstemmed | MUC1 aptamer-tethered H40-TEPA-PEG nanoconjugates for targeted siRNA-delivery and gene silencing in breast cancer cells |
| title_short | MUC1 aptamer-tethered H40-TEPA-PEG nanoconjugates for targeted siRNA-delivery and gene silencing in breast cancer cells |
| title_sort | muc1 aptamer tethered h40 tepa peg nanoconjugates for targeted sirna delivery and gene silencing in breast cancer cells |
| topic | mucin-1 bis-MPA polyester siRNA survivin breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2024.1383495/full |
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