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author:

Zhang, Bing-Chen (Zhang, Bing-Chen.) [1] | Lai, Chun-Mei (Lai, Chun-Mei.) [2] | Luo, Bang-Yue (Luo, Bang-Yue.) [3] | Shao, Jing-Wei (Shao, Jing-Wei.) [4] (Scholars:邵敬伟)

Indexed by:

Scopus SCIE CSCD

Abstract:

Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade (ICB) monotherapy. However, combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted delivery. Herein, based on a universal triterpene template and the anticancer active agent ursolic acid (UA), a cytomembrane-coated biomimetic delivery nanoplatform (UR@M) prepared by the selfassembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma (HCC) treatment. UR@M showed enhanced tumor accumulation in vivo with homologous tumor targeting, and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target effects. UA activated the natural immune system through the TLR2-MyD88-TRAF6 pathway, which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of PD-L1. The strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor regression. Overall, the UA-templated strategy "killed three birds with one stone" by establishing a self-assembly nanosystem, inducing tumor cell death, and promoting synergistic immunostimulation for HCC treatment.

Keyword:

Biomimetic nanoplatform CRISPR/Cas9 Gene therapy Hepatocellular carcinoma Immune checkpoint blockade Immunotherapy Self-assembly Ursolic acid

Community:

  • [ 1 ] [Zhang, Bing-Chen]Fuzhou Univ, Coll Chem, Fujian Prov Key Lab Canc Metastasis Chemoprevent &, Fuzhou 350116, Peoples R China
  • [ 2 ] [Lai, Chun-Mei]Fuzhou Univ, Coll Chem, Fujian Prov Key Lab Canc Metastasis Chemoprevent &, Fuzhou 350116, Peoples R China
  • [ 3 ] [Luo, Bang-Yue]Fuzhou Univ, Coll Chem, Fujian Prov Key Lab Canc Metastasis Chemoprevent &, Fuzhou 350116, Peoples R China
  • [ 4 ] [Shao, Jing-Wei]Fuzhou Univ, Coll Chem, Fujian Prov Key Lab Canc Metastasis Chemoprevent &, Fuzhou 350116, Peoples R China
  • [ 5 ] [Zhang, Bing-Chen]Southern Med Univ, Dongguan Peoples Hosp, Dongguan Inst Clin Canc Res, Dept Lab Med,Affiliated Hosp 10, Dongguan 523058, Peoples R China
  • [ 6 ] [Shao, Jing-Wei]Minjiang Univ, Coll Mat & Chem Engn, Fuzhou 350108, Peoples R China

Reprint 's Address:

  • [Shao, Jing-Wei]Fuzhou Univ, Coll Chem, Fujian Prov Key Lab Canc Metastasis Chemoprevent &, Fuzhou 350116, Peoples R China;;[Shao, Jing-Wei]Minjiang Univ, Coll Mat & Chem Engn, Fuzhou 350108, Peoples R China;;

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Source :

ACTA PHARMACEUTICA SINICA B

ISSN: 2211-3835

Year: 2024

Issue: 7

Volume: 14

Page: 3205-3217

1 4 . 8 0 0

JCR@2023

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 0

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