Therapeutic Nanocarriers Inhibit Chemotherapy‐Induced Breast Cancer Metastasis
Abstract Chemotherapy, although effective against primary tumors, may promote metastasis by causing the release of proinflammatory factors from damaged cells. Here, polymeric nanoparticles that deliver chemotherapeutics and scavenge proinflammatory factors simultaneously to inhibit chemotherapy‐indu...
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202203949 |
| _version_ | 1811179901424762880 |
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| author | Tianyu Li Tolulope Akinade Jie Zhou Hongxia Wang Qisong Tong Siyu He Emily Rinebold Luis E. Valencia Salazar Divya Bhansali Yiling Zhong Jing Ruan Jinzhi Du Piero Dalerba Kam W. Leong |
| author_facet | Tianyu Li Tolulope Akinade Jie Zhou Hongxia Wang Qisong Tong Siyu He Emily Rinebold Luis E. Valencia Salazar Divya Bhansali Yiling Zhong Jing Ruan Jinzhi Du Piero Dalerba Kam W. Leong |
| author_sort | Tianyu Li |
| collection | DOAJ |
| description | Abstract Chemotherapy, although effective against primary tumors, may promote metastasis by causing the release of proinflammatory factors from damaged cells. Here, polymeric nanoparticles that deliver chemotherapeutics and scavenge proinflammatory factors simultaneously to inhibit chemotherapy‐induced breast cancer metastasis are developed. The cationic nanoparticles can adsorb cell‐free nucleic acids (cfNAs) based on charge–charge interaction, which downregulates the expression of Toll‐like receptors and then reduces the secretion of inflammatory cytokines. Through in vitro structural optimization, cationic polyamidoamine (PAMAM) dendrimers modified with drug‐binding dodecyl groups and diethylethanolamine surface groups (PAMAM‐G3‐C125‐DEEA20) exhibit the most desirable combination of nanoparticle size (≈140 nm), drug loading, cytotoxicity, cfNA binding, and anti‐inflammatory activity. In the mouse models of breast cancer metastasis, paclitaxel‐loaded nanoparticles reduce serum levels of cfNAs and inflammatory cytokines compared with paclitaxel treatment alone and inhibit both primary tumor growth and tumor metastasis. Additionally, no significant side effects are detected in the serum or major organs. These results provide a strategy to deliver chemotherapeutics to primary tumors while reducing the prometastatic effects of chemotherapy. |
| first_indexed | 2024-04-11T06:41:32Z |
| format | Article |
| id | doaj.art-7960c2739a5e457ea83d73c43f73231d |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-11T06:41:32Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-7960c2739a5e457ea83d73c43f73231d2022-12-22T04:39:30ZengWileyAdvanced Science2198-38442022-11-01933n/an/a10.1002/advs.202203949Therapeutic Nanocarriers Inhibit Chemotherapy‐Induced Breast Cancer MetastasisTianyu Li0Tolulope Akinade1Jie Zhou2Hongxia Wang3Qisong Tong4Siyu He5Emily Rinebold6Luis E. Valencia Salazar7Divya Bhansali8Yiling Zhong9Jing Ruan10Jinzhi Du11Piero Dalerba12Kam W. Leong13Department of Biomedical Engineering Columbia University New York NY 10027 USAGraduate Program in Cellular, Molecular and Biomedical Studies Vagelos College of Physicians and Surgeons Columbia University New York NY 10027 USADepartment of Biomedical Engineering Columbia University New York NY 10027 USADepartment of Biomedical Engineering Columbia University New York NY 10027 USASchool of Biomedical Sciences and Engineering Guangzhou International Campus South China University of Technology Guangzhou 511442 P. R. ChinaDepartment of Biomedical Engineering Columbia University New York NY 10027 USADepartment of Pathology & Cell Biology Department of Medicine (Division of Digestive and Liver Diseases) Herbert Irving Comprehensive Cancer Center (HICCC) and Columbia Stem Cell Initiative (CSCI) Columbia University New York NY 10032 USADepartment of Pathology & Cell Biology Department of Medicine (Division of Digestive and Liver Diseases) Herbert Irving Comprehensive Cancer Center (HICCC) and Columbia Stem Cell Initiative (CSCI) Columbia University New York NY 10032 USADepartment of Biomedical Engineering Columbia University New York NY 10027 USADepartment of Biomedical Engineering Columbia University New York NY 10027 USADepartment of Biomedical Engineering Columbia University New York NY 10027 USASchool of Biomedical Sciences and Engineering Guangzhou International Campus South China University of Technology Guangzhou 511442 P. R. ChinaDepartment of Pathology & Cell Biology Department of Medicine (Division of Digestive and Liver Diseases) Herbert Irving Comprehensive Cancer Center (HICCC) and Columbia Stem Cell Initiative (CSCI) Columbia University New York NY 10032 USADepartment of Biomedical Engineering Columbia University New York NY 10027 USAAbstract Chemotherapy, although effective against primary tumors, may promote metastasis by causing the release of proinflammatory factors from damaged cells. Here, polymeric nanoparticles that deliver chemotherapeutics and scavenge proinflammatory factors simultaneously to inhibit chemotherapy‐induced breast cancer metastasis are developed. The cationic nanoparticles can adsorb cell‐free nucleic acids (cfNAs) based on charge–charge interaction, which downregulates the expression of Toll‐like receptors and then reduces the secretion of inflammatory cytokines. Through in vitro structural optimization, cationic polyamidoamine (PAMAM) dendrimers modified with drug‐binding dodecyl groups and diethylethanolamine surface groups (PAMAM‐G3‐C125‐DEEA20) exhibit the most desirable combination of nanoparticle size (≈140 nm), drug loading, cytotoxicity, cfNA binding, and anti‐inflammatory activity. In the mouse models of breast cancer metastasis, paclitaxel‐loaded nanoparticles reduce serum levels of cfNAs and inflammatory cytokines compared with paclitaxel treatment alone and inhibit both primary tumor growth and tumor metastasis. Additionally, no significant side effects are detected in the serum or major organs. These results provide a strategy to deliver chemotherapeutics to primary tumors while reducing the prometastatic effects of chemotherapy.https://doi.org/10.1002/advs.202203949breast cancercell‐free nucleic acidchemotherapymetastasisnanocarrierscavenger |
| spellingShingle | Tianyu Li Tolulope Akinade Jie Zhou Hongxia Wang Qisong Tong Siyu He Emily Rinebold Luis E. Valencia Salazar Divya Bhansali Yiling Zhong Jing Ruan Jinzhi Du Piero Dalerba Kam W. Leong Therapeutic Nanocarriers Inhibit Chemotherapy‐Induced Breast Cancer Metastasis Advanced Science breast cancer cell‐free nucleic acid chemotherapy metastasis nanocarrier scavenger |
| title | Therapeutic Nanocarriers Inhibit Chemotherapy‐Induced Breast Cancer Metastasis |
| title_full | Therapeutic Nanocarriers Inhibit Chemotherapy‐Induced Breast Cancer Metastasis |
| title_fullStr | Therapeutic Nanocarriers Inhibit Chemotherapy‐Induced Breast Cancer Metastasis |
| title_full_unstemmed | Therapeutic Nanocarriers Inhibit Chemotherapy‐Induced Breast Cancer Metastasis |
| title_short | Therapeutic Nanocarriers Inhibit Chemotherapy‐Induced Breast Cancer Metastasis |
| title_sort | therapeutic nanocarriers inhibit chemotherapy induced breast cancer metastasis |
| topic | breast cancer cell‐free nucleic acid chemotherapy metastasis nanocarrier scavenger |
| url | https://doi.org/10.1002/advs.202203949 |
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