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author:

Zhao, Rui-Rui (Zhao, Rui-Rui.) [1] | Wu, Ju-Hong (Wu, Ju-Hong.) [2] | Li, Jin -Yu (Li, Jin -Yu.) [3] (Scholars:李金宇) | Lu, Yu-sheng (Lu, Yu-sheng.) [4] | Shao, Jing -Wei (Shao, Jing -Wei.) [5] (Scholars:邵敬伟)

Indexed by:

EI Scopus SCIE

Abstract:

The heterogeneity of hepatocellular carcinoma (HCC) and the complexity of the tumor microenvironment (TME) pose challenges to efficient drug delivery and the antitumor efficacy of combined or synergistic therapies. Herein, a metal-coordinated carrier-free nanodrug (named as USFe3+ LA NPs) was developed for ferroptosis-mediated multimodal synergistic anti-HCC. Natural product ursolic acid (UA) was incorporated to enhance the sensitivity of tumor cells to sorafenib (SRF). Surface decoration of cell penetration peptide and epithelial cell adhesion molecule aptamer facilitated the uptake of USFe3+ LA NPs by HepG2 cells. Meanwhile, Fe3+ ions could react with intracellular hydrogen peroxide, generating toxic hydroxyl radical (& sdot;OH) for chemodynamical therapy (CDT) and amplified ferroptosis by cystine/glutamate antiporter system (System Xc  ), which promoted the consumption of glutathione (GSH) and inhibited the expression of glutathione peroxidase 4 (GPX4). Notably, these all-in-one nanodrugs could inhibit tumor metastasis and induced immunogenic cell death (ICD). Last but not least, the nanodrugs demonstrated favorable biocompatibility, augmenting the immune response against the programmed death-ligand 1 (PD-L1) by increasing cytotoxic T cell infiltration. In vivo studies revealed significant suppression of tumor growth and distant metastasis. Overall, our work introduced a novel strategy for applications of metalcoordinated co-assembled carrier-free nano-delivery system in HCC combination therapy, especially in the realms of cancer metastasis prevention and immunotherapy.

Keyword:

Chemodynamical therapy Ferroptosis Immunotherapy Metal -coordinated nanoplatform Synergistic chemotherapy

Community:

  • [ 1 ] [Zhao, Rui-Rui]Fuzhou Univ, Coll Chem, Fujian Prov Key Lab Canc Metastasis Chemoprevent &, Fuzhou 350108, Peoples R China
  • [ 2 ] [Shao, Jing -Wei]Fuzhou Univ, Coll Chem, Fujian Prov Key Lab Canc Metastasis Chemoprevent &, Fuzhou 350108, Peoples R China
  • [ 3 ] [Wu, Ju-Hong]Fuzhou Univ, Coll Chem, Natl & Local Joint Biomed Engn Res Ctr Photodynam, Fuzhou 350108, Peoples R China
  • [ 4 ] [Li, Jin -Yu]Fuzhou Univ, Coll Chem, Natl & Local Joint Biomed Engn Res Ctr Photodynam, Fuzhou 350108, Peoples R China
  • [ 5 ] [Lu, Yu-sheng]Minjiang Univ, Coll Mat & Chem Engn, Fujian Taiwan Hongkong Macao Sci & Technol Coopera, Fuzhou 350108, Fujian, Peoples R China
  • [ 6 ] [Shao, Jing -Wei]Minjiang Univ, Coll Mat & Chem Engn, Fujian Taiwan Hongkong Macao Sci & Technol Coopera, Fuzhou 350108, Fujian, Peoples R China

Reprint 's Address:

  • 邵敬伟

    [Shao, Jing -Wei]Fuzhou Univ, Coll Chem, Fujian Prov Key Lab Canc Metastasis Chemoprevent &, Fuzhou 350108, Peoples R China;;[Shao, Jing -Wei]Minjiang Univ, Coll Mat & Chem Engn, Fujian Taiwan Hongkong Macao Sci & Technol Coopera, Fuzhou 350108, Fujian, Peoples R China

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Source :

JOURNAL OF COLLOID AND INTERFACE SCIENCE

ISSN: 0021-9797

Year: 2024

Volume: 660

Page: 257-276

9 . 4 0 0

JCR@2023

Cited Count:

WoS CC Cited Count: 5

SCOPUS Cited Count: 5

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 1

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