The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer Model
Dendritic cell (DC) vaccines have recently been developed for the treatment of various cancers but often do not function as well as expected, primarily due to the highly complex in vivo immune environment. This proof-of-principle study aimed to test the feasibility of modulating the in vivo behavior...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-02-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.621642/full |
| _version_ | 1819275200630358016 |
|---|---|
| author | Changqiang Wu Changqiang Wu Wencheng Zhu Wencheng Zhu Rongrong Jin Hua Ai Ye Xu |
| author_facet | Changqiang Wu Changqiang Wu Wencheng Zhu Wencheng Zhu Rongrong Jin Hua Ai Ye Xu |
| author_sort | Changqiang Wu |
| collection | DOAJ |
| description | Dendritic cell (DC) vaccines have recently been developed for the treatment of various cancers but often do not function as well as expected, primarily due to the highly complex in vivo immune environment. This proof-of-principle study aimed to test the feasibility of modulating the in vivo behaviors of DC vaccines (DCVs) by introducing siRNA-laden magnetic resonance (MR) imaging nanovectors into cells, while providing visible information on their homing to lymph nodes. The N-alkyl-PEI2k-LAC/SPIO nanocomposites were prepared and characterized, showing favorable properties of siRNA transfection and MRI labeling efficiency in DCs. Cell viability assays revealed no observable effects on the survival and phenotype of DCs if the concentration of the complex was within 8 μg Fe/ml. An orthotopic mouse model of breast cancer was developed. The DCVs transfected with IDO siRNA contained nanocomposites were adoptively transferred to start the treatment. MR imaging clearly visualized the homing of DCVs into lymph nodes. At the end of the treatment, DCVs presented significantly better tumor suppression than DCs or PBS (P < 0.05). Generally, the N-alkyl-PEI2k-LAC/SPIO nanocomposites represent a highly efficient MR imaging platform for siRNA transfection that is potentially useful for in vivo tracking of vaccine cells. |
| first_indexed | 2024-12-23T23:20:33Z |
| format | Article |
| id | doaj.art-dac901ef89e94c2b887b608fb9dcb31f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-23T23:20:33Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-dac901ef89e94c2b887b608fb9dcb31f2022-12-21T17:26:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011010.3389/fonc.2020.621642621642The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer ModelChangqiang Wu0Changqiang Wu1Wencheng Zhu2Wencheng Zhu3Rongrong Jin4Hua Ai5Ye Xu6Department of Radiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, ChinaSichuan Key Laboratory of Medical Imaging and School of Medical Imaging, North Sichuan Medical College, Nanchong, ChinaNational Engineering Research Center for Biomaterials Sichuan University, Chengdu, ChinaShanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, ChinaNational Engineering Research Center for Biomaterials Sichuan University, Chengdu, ChinaNational Engineering Research Center for Biomaterials Sichuan University, Chengdu, ChinaDepartment of Radiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, ChinaDendritic cell (DC) vaccines have recently been developed for the treatment of various cancers but often do not function as well as expected, primarily due to the highly complex in vivo immune environment. This proof-of-principle study aimed to test the feasibility of modulating the in vivo behaviors of DC vaccines (DCVs) by introducing siRNA-laden magnetic resonance (MR) imaging nanovectors into cells, while providing visible information on their homing to lymph nodes. The N-alkyl-PEI2k-LAC/SPIO nanocomposites were prepared and characterized, showing favorable properties of siRNA transfection and MRI labeling efficiency in DCs. Cell viability assays revealed no observable effects on the survival and phenotype of DCs if the concentration of the complex was within 8 μg Fe/ml. An orthotopic mouse model of breast cancer was developed. The DCVs transfected with IDO siRNA contained nanocomposites were adoptively transferred to start the treatment. MR imaging clearly visualized the homing of DCVs into lymph nodes. At the end of the treatment, DCVs presented significantly better tumor suppression than DCs or PBS (P < 0.05). Generally, the N-alkyl-PEI2k-LAC/SPIO nanocomposites represent a highly efficient MR imaging platform for siRNA transfection that is potentially useful for in vivo tracking of vaccine cells.https://www.frontiersin.org/articles/10.3389/fonc.2020.621642/fulldendritic cellanticancer immunotherapygene transfectionnanocompositemagnetic resonance imaging |
| spellingShingle | Changqiang Wu Changqiang Wu Wencheng Zhu Wencheng Zhu Rongrong Jin Hua Ai Ye Xu The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer Model Frontiers in Oncology dendritic cell anticancer immunotherapy gene transfection nanocomposite magnetic resonance imaging |
| title | The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer Model |
| title_full | The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer Model |
| title_fullStr | The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer Model |
| title_full_unstemmed | The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer Model |
| title_short | The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer Model |
| title_sort | mri visible nanocomposite facilitates the delivery and tracking of sirna loaded dc vaccine in the breast cancer model |
| topic | dendritic cell anticancer immunotherapy gene transfection nanocomposite magnetic resonance imaging |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.621642/full |
| work_keys_str_mv | AT changqiangwu themrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT changqiangwu themrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT wenchengzhu themrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT wenchengzhu themrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT rongrongjin themrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT huaai themrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT yexu themrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT changqiangwu mrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT changqiangwu mrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT wenchengzhu mrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT wenchengzhu mrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT rongrongjin mrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT huaai mrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel AT yexu mrivisiblenanocompositefacilitatesthedeliveryandtrackingofsirnaloadeddcvaccineinthebreastcancermodel |