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author：

Zhang, D. (Zhang, D..) [1] | Jiang, C. (Jiang, C..) [2] | Zheng, X. (Zheng, X..) [3] | Lin, Z. (Lin, Z..) [4] | Zhuang, Q. (Zhuang, Q..) [5] | Xie, H. (Xie, H..) [6] | Liang, Y. (Liang, Y..) [7] | Xu, Y. (Xu, Y..) [8] | Cui, L. (Cui, L..) [9] | Liu, X. (Liu, X..) [10] | Zeng, Y. (Zeng, Y..) [11]

Indexed by：

Scopus

Abstract：

Immunocheckpoint　inhibitors　combined　with　Lenvatinib　is　the　first　line　treatment　for　hepatocellular　carcinoma　(HCC),　but　their　potency　is　hampered　by　the　low　response　rate　and　adverse　events.　Herein,　a　targeted　therapeutic　strategy　through　the　coassembly　of　Lenvatinib,　Adriamycin,　Fe3+　ion,　and　a　natural　polyphenol　(metallo-nanodrugs)　is　presented　by　coordination　effect　for　potentiating　tumor　vascular　normalization　and　systematic　chemo-immunotherapy　to　effectively　inhibit　the　progression　of　HCC　in　both　orthotopic　model　and　patients-derived　organoids.　In　mice　with　orthotopic　HCC,　the　obtained　metallo-nanodrugs　efficiently　increase　the　drug　accumulation　in　orthotopic　tumors　and　can　respond　to　acidic　tumor　environment.　The　promotion　of　tumor　vascular　normalization　by　metallo-nanodrugs　is　observed,　which　enhances　the　infiltrating　T　lymphocytes　in　tumor,　and　reinforces　the　calreticulin-mediated　antitumor　immunity　through　alleviating　hypoxia,　reducing　regulatory　T　cells,　and　down-regulating　PDL1　expression　of　tumors.　The　excellent　therapeutic　efficiency　with　complete　remission　of　orthotopic　tumors　(3/6)　and　long-term　survival　of　mice　(4/6,　42　days)　are　also　achieved.　Furthermore,　the　excellent　therapeutic　effect　of　metallo-nanodrugs　is　also　validated　in　5　patient-derived　organoids,　and　hence　can　provide　a　marvelous　systemic　chemo-immunotherapy　strategy　for　enhancing　HCC　treatment.　©　2023　Wiley-VCH　GmbH.

Keyword：

calreticulin coordination nanoparticles hepatocellular carcinoma lenvatinib organoids vascular normalization

Community：

  • [ 1 ] [Zhang D.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 2 ] [Zhang D.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 3 ] [Jiang C.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 4 ] [Zheng X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 5 ] [Lin Z.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 6 ] [Lin Z.]Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China
  • [ 7 ] [Zhuang Q.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 8 ] [Zhuang Q.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 9 ] [Xie H.]Fujian Key Laboratory of Functional Marine Sensing Materials, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, 350108, China
  • [ 10 ] [Liang Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 11 ] [Xu Y.]Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
  • [ 12 ] [Cui L.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 13 ] [Cui L.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 14 ] [Liu X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 15 ] [Liu X.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 16 ] [Liu X.]CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China
  • [ 17 ] [Zeng Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 18 ] [Zeng Y.]Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China

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Small

ISSN： 1613-6810

Year： 2023

Issue： 29

Volume： 19

1 3 . 0

JCR@2023

1 3 . 0 0 0

JCR@2023

ESI HC Threshold：49

JCR Journal Grade：1

CAS Journal Grade：1

Cited Count：

WoS CC Cited Count： 0

SCOPUS Cited Count： 17

ESI Highly Cited Papers on the List： 0 Unfold All

WanFang Cited Count：

Chinese Cited Count：

30 Days PV： 3

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