Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of glioma
Currently, combination drug therapy is one of the most effective approaches to glioma treatment. However, due to the inherent dissimilar pharmacokinetics of individual drugs and blood brain barriers, it was difficult for the concomitant drugs to simultaneously be delivered to glioma in an optimal do...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Drug Delivery |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/10717544.2018.1474974 |
| _version_ | 1818329112366809088 |
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| author | He-Lin Xu Zi-Liang Fan De-Li ZhuGe Meng-Qi Tong Bi-Xin Shen Meng-Ting Lin Qun-Yan Zhu Bing-Hui Jin Yasin Sohawon Qing Yao Ying-Zheng Zhao |
| author_facet | He-Lin Xu Zi-Liang Fan De-Li ZhuGe Meng-Qi Tong Bi-Xin Shen Meng-Ting Lin Qun-Yan Zhu Bing-Hui Jin Yasin Sohawon Qing Yao Ying-Zheng Zhao |
| author_sort | He-Lin Xu |
| collection | DOAJ |
| description | Currently, combination drug therapy is one of the most effective approaches to glioma treatment. However, due to the inherent dissimilar pharmacokinetics of individual drugs and blood brain barriers, it was difficult for the concomitant drugs to simultaneously be delivered to glioma in an optimal dose ratio manner. Herein, a cationic micellar core (Cur-M) was first prepared from d-α-tocopherol-grafted-ε-polylysine polymer to encapsulate the hydrophobic curcumin, followed by dopamine-modified-poly-γ-glutamic acid polymer further deposited on its surface as a anion shell through pH-sensitive linkage to encapsulate the hydrophilic doxorubicin (DOX) hydrochloride. By controlling the combinational Cur/DOX molar ratio at 3:1, a pH-sensitive core–shell nanoparticle (PDCP-NP) was constructed to simultaneously target the cancer stem cells (CSCs) and the differentiated tumor cells. PDCP-NP exhibited a dynamic diameter of 160.8 nm and a zeta-potential of –30.5 mV, while its core–shell structure was further confirmed by XPS and TEM. The ratiometric delivery capability of PDCP-NP was confirmed by in vitro and in vivo studies, in comparison with the cocktail Cur/DOX solution. Meanwhile, the percentage of CSCs in tumors was significantly decreased from 4.16% to 0.95% after treatment with PDCP-NP. Overall, PDCP-NP may be a promising carrier for the combination therapy with drug candidates having dissimilar physicochemical properties. |
| first_indexed | 2024-12-13T12:42:53Z |
| format | Article |
| id | doaj.art-ea3a4d08c54549b992d3b44a5081640b |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-13T12:42:53Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-ea3a4d08c54549b992d3b44a5081640b2022-12-21T23:45:35ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642018-01-012511302131810.1080/10717544.2018.14749741474974Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of gliomaHe-Lin Xu0Zi-Liang Fan1De-Li ZhuGe2Meng-Qi Tong3Bi-Xin Shen4Meng-Ting Lin5Qun-Yan Zhu6Bing-Hui Jin7Yasin Sohawon8Qing Yao9Ying-Zheng Zhao10Wenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityCurrently, combination drug therapy is one of the most effective approaches to glioma treatment. However, due to the inherent dissimilar pharmacokinetics of individual drugs and blood brain barriers, it was difficult for the concomitant drugs to simultaneously be delivered to glioma in an optimal dose ratio manner. Herein, a cationic micellar core (Cur-M) was first prepared from d-α-tocopherol-grafted-ε-polylysine polymer to encapsulate the hydrophobic curcumin, followed by dopamine-modified-poly-γ-glutamic acid polymer further deposited on its surface as a anion shell through pH-sensitive linkage to encapsulate the hydrophilic doxorubicin (DOX) hydrochloride. By controlling the combinational Cur/DOX molar ratio at 3:1, a pH-sensitive core–shell nanoparticle (PDCP-NP) was constructed to simultaneously target the cancer stem cells (CSCs) and the differentiated tumor cells. PDCP-NP exhibited a dynamic diameter of 160.8 nm and a zeta-potential of –30.5 mV, while its core–shell structure was further confirmed by XPS and TEM. The ratiometric delivery capability of PDCP-NP was confirmed by in vitro and in vivo studies, in comparison with the cocktail Cur/DOX solution. Meanwhile, the percentage of CSCs in tumors was significantly decreased from 4.16% to 0.95% after treatment with PDCP-NP. Overall, PDCP-NP may be a promising carrier for the combination therapy with drug candidates having dissimilar physicochemical properties.http://dx.doi.org/10.1080/10717544.2018.1474974ratiometric deliverydissimilar pharmacokineticscombination therapyheterogeneitytargeting |
| spellingShingle | He-Lin Xu Zi-Liang Fan De-Li ZhuGe Meng-Qi Tong Bi-Xin Shen Meng-Ting Lin Qun-Yan Zhu Bing-Hui Jin Yasin Sohawon Qing Yao Ying-Zheng Zhao Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of glioma Drug Delivery ratiometric delivery dissimilar pharmacokinetics combination therapy heterogeneity targeting |
| title | Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of glioma |
| title_full | Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of glioma |
| title_fullStr | Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of glioma |
| title_full_unstemmed | Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of glioma |
| title_short | Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of glioma |
| title_sort | ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through ph sensitive core shell nanoparticles targeting the heterogeneous tumor cells of glioma |
| topic | ratiometric delivery dissimilar pharmacokinetics combination therapy heterogeneity targeting |
| url | http://dx.doi.org/10.1080/10717544.2018.1474974 |
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