Clathrin light chain-conjugated drug delivery for cancer

Sungwook Jung; Liwei Jiang; Jing Zhao; Leonard D. Shultz; Dale L. Greiner; Munhyung Bae; Xiaofei Li; Farideh Ordikhani; Rui Kuai; John Joseph; Vivek Kasinath; David R. Elmaleh; Reza Abdi

doi:10.1002/btm2.10273

Clathrin light chain-conjugated drug delivery for cancer

Sungwook Jung, Liwei Jiang, Jing Zhao, Leonard D. Shultz, Dale L. Greiner, Munhyung Bae, Xiaofei Li, Farideh Ordikhani, Rui Kuai, John Joseph, Vivek Kasinath, David R. Elmaleh, Reza Abdi

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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.

Original language	English
Article number	e10273
Journal	Bioengineering and Translational Medicine
Volume	8
Issue number	1
DOIs	https://doi.org/10.1002/btm2.10273
State	Published - Jan 2023
Externally published	Yes

Keywords

cancer
drug delivery
fluorescence imaging
targeted therapy

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10.1002/btm2.10273

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title = "Clathrin light chain-conjugated drug delivery for cancer",

abstract = "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.",

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year = "2023",

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AU - Jung, Sungwook

AU - Jiang, Liwei

AU - Zhao, Jing

AU - Shultz, Leonard D.

AU - Greiner, Dale L.

AU - Bae, Munhyung

AU - Li, Xiaofei

AU - Ordikhani, Farideh

AU - Kuai, Rui

AU - Joseph, John

AU - Kasinath, Vivek

AU - Elmaleh, David R.

AU - Abdi, Reza

PY - 2023/1

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N2 - 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.

AB - 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.

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Clathrin light chain-conjugated drug delivery for cancer

Abstract

Keywords

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