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 journalArticlepeer-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 languageEnglish
    Article number2003891
    JournalAdvanced Functional Materials
    Volume30
    Issue number43
    DOIs
    Publication statusPublished - 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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