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Clathrin light chain‐conjugated drug delivery for cancer
Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)‐conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a gluta...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842032/ https://www.ncbi.nlm.nih.gov/pubmed/36684105 http://dx.doi.org/10.1002/btm2.10273 |
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author | Jung, Sungwook Jiang, Liwei Zhao, Jing Shultz, Leonard D. Greiner, Dale L. Bae, Munhyung Li, Xiaofei Ordikhani, Farideh Kuai, Rui Joseph, John Kasinath, Vivek Elmaleh, David R. Abdi, Reza |
author_facet | Jung, Sungwook Jiang, Liwei Zhao, Jing Shultz, Leonard D. Greiner, Dale L. Bae, Munhyung Li, Xiaofei Ordikhani, Farideh Kuai, Rui Joseph, John Kasinath, Vivek Elmaleh, David R. Abdi, Reza |
author_sort | Jung, Sungwook |
collection | PubMed |
description | Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)‐conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a glutaric anhydride at high efficiency. Labeled CLCs localized to 4T1 tumors implanted in mice, and conjugation of PTX to CLC enhanced its delivery to these tumors. Treatment of three different mouse models of cancer—melanoma, breast cancer, and lung cancer—with CLC‐PTX resulted in significant growth inhibition of both the primary tumor and metastatic lesions, as compared to treatment with free PTX. CLC‐PTX treatment caused a marked increase in apoptosis of tumor cells and reduction of tumor angiogenesis. Our data suggested HSP70 as a binding partner for CLC. Our study demonstrates that CLC‐based drug‐conjugates constitute a novel drug delivery platform that can augment the effects of chemotherapeutics in treating a variety of cancers. Moreover, conjugation of therapeutics with CLC may be used as means by which drugs are delivered specifically to primary tumors and metastatic lesions, thereby prolonging the survival of cancer patients. |
format | Online Article Text |
id | pubmed-9842032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98420322023-01-19 Clathrin light chain‐conjugated drug delivery for cancer Jung, Sungwook Jiang, Liwei Zhao, Jing Shultz, Leonard D. Greiner, Dale L. Bae, Munhyung Li, Xiaofei Ordikhani, Farideh Kuai, Rui Joseph, John Kasinath, Vivek Elmaleh, David R. Abdi, Reza Bioeng Transl Med Research Articles Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)‐conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a glutaric anhydride at high efficiency. Labeled CLCs localized to 4T1 tumors implanted in mice, and conjugation of PTX to CLC enhanced its delivery to these tumors. Treatment of three different mouse models of cancer—melanoma, breast cancer, and lung cancer—with CLC‐PTX resulted in significant growth inhibition of both the primary tumor and metastatic lesions, as compared to treatment with free PTX. CLC‐PTX treatment caused a marked increase in apoptosis of tumor cells and reduction of tumor angiogenesis. Our data suggested HSP70 as a binding partner for CLC. Our study demonstrates that CLC‐based drug‐conjugates constitute a novel drug delivery platform that can augment the effects of chemotherapeutics in treating a variety of cancers. Moreover, conjugation of therapeutics with CLC may be used as means by which drugs are delivered specifically to primary tumors and metastatic lesions, thereby prolonging the survival of cancer patients. John Wiley & Sons, Inc. 2022-11-28 /pmc/articles/PMC9842032/ /pubmed/36684105 http://dx.doi.org/10.1002/btm2.10273 Text en © 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Jung, Sungwook Jiang, Liwei Zhao, Jing Shultz, Leonard D. Greiner, Dale L. Bae, Munhyung Li, Xiaofei Ordikhani, Farideh Kuai, Rui Joseph, John Kasinath, Vivek Elmaleh, David R. Abdi, Reza Clathrin light chain‐conjugated drug delivery for cancer |
title | Clathrin light chain‐conjugated drug delivery for cancer |
title_full | Clathrin light chain‐conjugated drug delivery for cancer |
title_fullStr | Clathrin light chain‐conjugated drug delivery for cancer |
title_full_unstemmed | Clathrin light chain‐conjugated drug delivery for cancer |
title_short | Clathrin light chain‐conjugated drug delivery for cancer |
title_sort | clathrin light chain‐conjugated drug delivery for cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842032/ https://www.ncbi.nlm.nih.gov/pubmed/36684105 http://dx.doi.org/10.1002/btm2.10273 |
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