Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapy
Chemotherapy is currently an irreplaceable strategy for cancer treatment. Doxorubicin hydrochloride (DOX) is a clinical first-line drug for cancer chemotherapy. While its efficacy for cancer treatment is greatly compromised due to invalid enrichment or serious side effects. To increase the content o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Drug Delivery |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/10717544.2021.1986602 |
| _version_ | 1818334103676649472 |
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| author | Lei Qiao Xue Yuan Hui Peng Guisong Shan Min Gao Xiaoqing Yi Xiaoyan He |
| author_facet | Lei Qiao Xue Yuan Hui Peng Guisong Shan Min Gao Xiaoqing Yi Xiaoyan He |
| author_sort | Lei Qiao |
| collection | DOAJ |
| description | Chemotherapy is currently an irreplaceable strategy for cancer treatment. Doxorubicin hydrochloride (DOX) is a clinical first-line drug for cancer chemotherapy. While its efficacy for cancer treatment is greatly compromised due to invalid enrichment or serious side effects. To increase the content of intracellular targets and boost the antitumor effect of DOX, a novel biotinylated hyaluronic acid-guided dual-functionalized CaCO3-based drug delivery system (DOX@BHNP) with target specificity and acid-triggered drug-releasing capability was synthesized. The ability of the drug delivery system on enriching DOX in mitochondria and nucleus, which further cause significant tumor inhibition, were investigated to provide a more comprehensive understanding of this CaCO3-based drug delivery system. After targeted endocytosis by tumor cells, DOX could release faster in the weakly acidic lysosome, and further enrich in mitochondria and nucleus, which cause mitochondrial destruction and nuclear DNA leakage, and result in cell cycle arrest and cell apoptosis. Virtually, an effective tumor inhibition was observed in vitro and in vivo. More importantly, the batch-to-batch variation of DOX loading level in the DOX@BHNP system is negligible, and no obvious histological changes in the main organs were observed, indicating the promising application of this functionalized drug delivery system in cancer treatment. |
| first_indexed | 2024-12-13T14:02:13Z |
| format | Article |
| id | doaj.art-0dbb522307d84eccb89177a2a055bc6c |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-13T14:02:13Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-0dbb522307d84eccb89177a2a055bc6c2022-12-21T23:42:42ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642021-01-012812218222810.1080/10717544.2021.19866021986602Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapyLei Qiao0Xue Yuan1Hui Peng2Guisong Shan3Min Gao4Xiaoqing Yi5Xiaoyan He6School of Basic Medical Sciences, Anhui Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Life Sciences, Anhui Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Life Sciences, Anhui Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Life Sciences, Anhui Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical UniversityKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Life Sciences, Anhui Medical UniversityChemotherapy is currently an irreplaceable strategy for cancer treatment. Doxorubicin hydrochloride (DOX) is a clinical first-line drug for cancer chemotherapy. While its efficacy for cancer treatment is greatly compromised due to invalid enrichment or serious side effects. To increase the content of intracellular targets and boost the antitumor effect of DOX, a novel biotinylated hyaluronic acid-guided dual-functionalized CaCO3-based drug delivery system (DOX@BHNP) with target specificity and acid-triggered drug-releasing capability was synthesized. The ability of the drug delivery system on enriching DOX in mitochondria and nucleus, which further cause significant tumor inhibition, were investigated to provide a more comprehensive understanding of this CaCO3-based drug delivery system. After targeted endocytosis by tumor cells, DOX could release faster in the weakly acidic lysosome, and further enrich in mitochondria and nucleus, which cause mitochondrial destruction and nuclear DNA leakage, and result in cell cycle arrest and cell apoptosis. Virtually, an effective tumor inhibition was observed in vitro and in vivo. More importantly, the batch-to-batch variation of DOX loading level in the DOX@BHNP system is negligible, and no obvious histological changes in the main organs were observed, indicating the promising application of this functionalized drug delivery system in cancer treatment.http://dx.doi.org/10.1080/10717544.2021.1986602chemotherapycaco3targeted deliveryacid-responsemitochondrianucleus |
| spellingShingle | Lei Qiao Xue Yuan Hui Peng Guisong Shan Min Gao Xiaoqing Yi Xiaoyan He Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapy Drug Delivery chemotherapy caco3 targeted delivery acid-response mitochondria nucleus |
| title | Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapy |
| title_full | Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapy |
| title_fullStr | Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapy |
| title_full_unstemmed | Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapy |
| title_short | Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapy |
| title_sort | targeted delivery and stimulus responsive release of anticancer drugs for efficient chemotherapy |
| topic | chemotherapy caco3 targeted delivery acid-response mitochondria nucleus |
| url | http://dx.doi.org/10.1080/10717544.2021.1986602 |
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