Emetine-Loaded Black Phosphorus Hydrogel Sensitizes Tumor to Photothermal Therapy through Inhibition of Stress Granule Formation

Jianlei Xie; Taojian Fan; Ji Hyeon Kim; Yunjie Xu; Yingwei Wang; Weiyuan Liang; Lijun Qiao; Zongze Wu; Quan Liu; Weibin Hu; Na Yin; Ling Yang; Liping Liu; Jong Seung Kim; Han Zhang

doi:10.1002/adfm.202003891

Emetine-Loaded Black Phosphorus Hydrogel Sensitizes Tumor to Photothermal Therapy through Inhibition of Stress Granule Formation

Jianlei Xie, Taojian Fan, Ji Hyeon Kim, Yunjie Xu, Yingwei Wang, Weiyuan Liang, Lijun Qiao, Zongze Wu, Quan Liu, Weibin Hu, Na Yin, Ling Yang, Liping Liu, Jong Seung Kim, Han Zhang

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

49 Citations (Scopus)

Abstract

During photothermal therapy (PTT), hyperthermia up to 50 °C is required for efficient induction of tumor cell death. Additional increases in temperature can lead to severe damage to adjacent tissues. Conversely, insufficient heating of deep-seated tumor tissues results in tumor recurrence. Sensitization of tumor cells to PTT may solve this problem. Stress granules (SGs) function in integration of various internal and external stresses to regulate cell viability. However, the role of SGs in PTT is currently unknown. Here, with black phosphorus (BP) nanosheets as photothermal agents, it is found that SGs are induced in tumor by PTT through eukaryotic initiation factor 2α-dependent pathway and participate in tumor resistance to PTT. To modulate SG formation in tumor, a BP hydrogel is prepared for tumor-specific delivery and near-infrared (NIR) light-controlled release of the SG inhibitor Emetine. Upon NIR-light irradiation, photothermal conversion of BP nanosheets enables PTT of tumor. Meanwhile, light-controlled release of Emetine in tumor tissues effectively inhibits PTT-induced SG formation and sensitizes tumor to PTT, resulting in enhanced tumor inhibition. These results reveal the role of SGs in PTT and present a novel strategy for tumor sensitization to enhance the therapeutic efficacy and reduce the side effects of PTT.

Original language	English
Article number	2003891
Journal	Advanced Functional Materials
Volume	30
Issue number	43
DOIs	https://doi.org/10.1002/adfm.202003891
Publication status	Published - 2020 Oct 1

Bibliographical note

Funding Information:
J.X. and T.F. contributed equally to this work. This work was supported by the State Key Research Development Program of China (Grant No. 2019YFB2203503), National Natural Science Fund (Grant Nos. 61875138, 61961136001, and U1801254), Science and Technology Innovation Commission of Shenzhen (KQTD2015032416270385, JCYJ20170811093453105, JCYJ20180307164612205, and GJHZ20180928160209731), and the National Research Foundation of Korea (Grant No. 2018R1A3B1052702, JSK). Authors also acknowledge the support from Instrumental Analysis Center of Shenzhen University (Xili Campus).

Funding Information:
J.X. and T.F. contributed equally to this work. This work was supported by the State Key Research Development Program of China (Grant No. 2019YFB2203503), National Natural Science Fund (Grant Nos. 61875138, 61961136001, and U1801254), Science and Technology Innovation Commission of Shenzhen (KQTD2015032416270385, JCYJ20170811093453105, JCYJ20180307164612205, and GJHZ20180928160209731), and the National Research Foundation of Korea (Grant No. 2018R1A3B1052702, JSK). Authors also acknowledge the support from Instrumental Analysis Center of Shenzhen University (Xili Campus).

Publisher Copyright:
© 2020 Wiley-VCH GmbH

Keywords

Emetine
black phosphorus hydrogel
photothermal therapy
stress granules
tumor sensitization

ASJC Scopus subject areas

General Chemistry
General Materials Science
Condensed Matter Physics

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10.1002/adfm.202003891

Cite this

Xie, J., Fan, T., Kim, J. H., Xu, Y., Wang, Y., Liang, W., Qiao, L., Wu, Z., Liu, Q., Hu, W., Yin, N., Yang, L., Liu, L., Kim, J. S., & Zhang, H. (2020). Emetine-Loaded Black Phosphorus Hydrogel Sensitizes Tumor to Photothermal Therapy through Inhibition of Stress Granule Formation. Advanced Functional Materials, 30(43), Article 2003891. https://doi.org/10.1002/adfm.202003891

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title = "Emetine-Loaded Black Phosphorus Hydrogel Sensitizes Tumor to Photothermal Therapy through Inhibition of Stress Granule Formation",

abstract = "During photothermal therapy (PTT), hyperthermia up to 50 °C is required for efficient induction of tumor cell death. Additional increases in temperature can lead to severe damage to adjacent tissues. Conversely, insufficient heating of deep-seated tumor tissues results in tumor recurrence. Sensitization of tumor cells to PTT may solve this problem. Stress granules (SGs) function in integration of various internal and external stresses to regulate cell viability. However, the role of SGs in PTT is currently unknown. Here, with black phosphorus (BP) nanosheets as photothermal agents, it is found that SGs are induced in tumor by PTT through eukaryotic initiation factor 2α-dependent pathway and participate in tumor resistance to PTT. To modulate SG formation in tumor, a BP hydrogel is prepared for tumor-specific delivery and near-infrared (NIR) light-controlled release of the SG inhibitor Emetine. Upon NIR-light irradiation, photothermal conversion of BP nanosheets enables PTT of tumor. Meanwhile, light-controlled release of Emetine in tumor tissues effectively inhibits PTT-induced SG formation and sensitizes tumor to PTT, resulting in enhanced tumor inhibition. These results reveal the role of SGs in PTT and present a novel strategy for tumor sensitization to enhance the therapeutic efficacy and reduce the side effects of PTT.",

keywords = "Emetine, black phosphorus hydrogel, photothermal therapy, stress granules, tumor sensitization",

author = "Jianlei Xie and Taojian Fan and Kim, {Ji Hyeon} and Yunjie Xu and Yingwei Wang and Weiyuan Liang and Lijun Qiao and Zongze Wu and Quan Liu and Weibin Hu and Na Yin and Ling Yang and Liping Liu and Kim, {Jong Seung} and Han Zhang",

note = "Funding Information: J.X. and T.F. contributed equally to this work. This work was supported by the State Key Research Development Program of China (Grant No. 2019YFB2203503), National Natural Science Fund (Grant Nos. 61875138, 61961136001, and U1801254), Science and Technology Innovation Commission of Shenzhen (KQTD2015032416270385, JCYJ20170811093453105, JCYJ20180307164612205, and GJHZ20180928160209731), and the National Research Foundation of Korea (Grant No. 2018R1A3B1052702, JSK). Authors also acknowledge the support from Instrumental Analysis Center of Shenzhen University (Xili Campus). Funding Information: J.X. and T.F. contributed equally to this work. This work was supported by the State Key Research Development Program of China (Grant No. 2019YFB2203503), National Natural Science Fund (Grant Nos. 61875138, 61961136001, and U1801254), Science and Technology Innovation Commission of Shenzhen (KQTD2015032416270385, JCYJ20170811093453105, JCYJ20180307164612205, and GJHZ20180928160209731), and the National Research Foundation of Korea (Grant No. 2018R1A3B1052702, JSK). Authors also acknowledge the support from Instrumental Analysis Center of Shenzhen University (Xili Campus). Publisher Copyright: {\textcopyright} 2020 Wiley-VCH GmbH",

year = "2020",

month = oct,

day = "1",

doi = "10.1002/adfm.202003891",

language = "English",

volume = "30",

journal = "Advanced Functional Materials",

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T1 - Emetine-Loaded Black Phosphorus Hydrogel Sensitizes Tumor to Photothermal Therapy through Inhibition of Stress Granule Formation

AU - Xie, Jianlei

AU - Fan, Taojian

AU - Kim, Ji Hyeon

AU - Xu, Yunjie

AU - Wang, Yingwei

AU - Liang, Weiyuan

AU - Qiao, Lijun

AU - Wu, Zongze

AU - Liu, Quan

AU - Hu, Weibin

AU - Yin, Na

AU - Yang, Ling

AU - Liu, Liping

AU - Kim, Jong Seung

AU - Zhang, Han

N1 - Funding Information: J.X. and T.F. contributed equally to this work. This work was supported by the State Key Research Development Program of China (Grant No. 2019YFB2203503), National Natural Science Fund (Grant Nos. 61875138, 61961136001, and U1801254), Science and Technology Innovation Commission of Shenzhen (KQTD2015032416270385, JCYJ20170811093453105, JCYJ20180307164612205, and GJHZ20180928160209731), and the National Research Foundation of Korea (Grant No. 2018R1A3B1052702, JSK). Authors also acknowledge the support from Instrumental Analysis Center of Shenzhen University (Xili Campus). Funding Information: J.X. and T.F. contributed equally to this work. This work was supported by the State Key Research Development Program of China (Grant No. 2019YFB2203503), National Natural Science Fund (Grant Nos. 61875138, 61961136001, and U1801254), Science and Technology Innovation Commission of Shenzhen (KQTD2015032416270385, JCYJ20170811093453105, JCYJ20180307164612205, and GJHZ20180928160209731), and the National Research Foundation of Korea (Grant No. 2018R1A3B1052702, JSK). Authors also acknowledge the support from Instrumental Analysis Center of Shenzhen University (Xili Campus). Publisher Copyright: © 2020 Wiley-VCH GmbH

PY - 2020/10/1

Y1 - 2020/10/1

N2 - During photothermal therapy (PTT), hyperthermia up to 50 °C is required for efficient induction of tumor cell death. Additional increases in temperature can lead to severe damage to adjacent tissues. Conversely, insufficient heating of deep-seated tumor tissues results in tumor recurrence. Sensitization of tumor cells to PTT may solve this problem. Stress granules (SGs) function in integration of various internal and external stresses to regulate cell viability. However, the role of SGs in PTT is currently unknown. Here, with black phosphorus (BP) nanosheets as photothermal agents, it is found that SGs are induced in tumor by PTT through eukaryotic initiation factor 2α-dependent pathway and participate in tumor resistance to PTT. To modulate SG formation in tumor, a BP hydrogel is prepared for tumor-specific delivery and near-infrared (NIR) light-controlled release of the SG inhibitor Emetine. Upon NIR-light irradiation, photothermal conversion of BP nanosheets enables PTT of tumor. Meanwhile, light-controlled release of Emetine in tumor tissues effectively inhibits PTT-induced SG formation and sensitizes tumor to PTT, resulting in enhanced tumor inhibition. These results reveal the role of SGs in PTT and present a novel strategy for tumor sensitization to enhance the therapeutic efficacy and reduce the side effects of PTT.

AB - During photothermal therapy (PTT), hyperthermia up to 50 °C is required for efficient induction of tumor cell death. Additional increases in temperature can lead to severe damage to adjacent tissues. Conversely, insufficient heating of deep-seated tumor tissues results in tumor recurrence. Sensitization of tumor cells to PTT may solve this problem. Stress granules (SGs) function in integration of various internal and external stresses to regulate cell viability. However, the role of SGs in PTT is currently unknown. Here, with black phosphorus (BP) nanosheets as photothermal agents, it is found that SGs are induced in tumor by PTT through eukaryotic initiation factor 2α-dependent pathway and participate in tumor resistance to PTT. To modulate SG formation in tumor, a BP hydrogel is prepared for tumor-specific delivery and near-infrared (NIR) light-controlled release of the SG inhibitor Emetine. Upon NIR-light irradiation, photothermal conversion of BP nanosheets enables PTT of tumor. Meanwhile, light-controlled release of Emetine in tumor tissues effectively inhibits PTT-induced SG formation and sensitizes tumor to PTT, resulting in enhanced tumor inhibition. These results reveal the role of SGs in PTT and present a novel strategy for tumor sensitization to enhance the therapeutic efficacy and reduce the side effects of PTT.

KW - Emetine

KW - black phosphorus hydrogel

KW - photothermal therapy

KW - stress granules

KW - tumor sensitization

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DO - 10.1002/adfm.202003891

M3 - Article

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SN - 1616-301X

VL - 30

JO - Advanced Functional Materials

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M1 - 2003891

ER -

Emetine-Loaded Black Phosphorus Hydrogel Sensitizes Tumor to Photothermal Therapy through Inhibition of Stress Granule Formation

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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