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  Bimodal treatment of hepatocellular carcinoma by targeted minimally interventional photodynamic/chemotherapy using glyco-covalent-organic frameworks-guided porphyrin/sorafenib

Hu, J., Hu, J., Wu, W., Qin, Y., Fu, J., Liu, C., et al. (2022). Bimodal treatment of hepatocellular carcinoma by targeted minimally interventional photodynamic/chemotherapy using glyco-covalent-organic frameworks-guided porphyrin/sorafenib. Acta Biomaterialia, 148, 206-217. doi:10.1016/j.actbio.2022.06.012.

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 Creators:
Hu, Jun, Author
Hu, Jing, Author
Wu, Wenrui, Author
Qin, Yufei, Author
Fu, Junjie, Author
Liu, Chao, Author
Seeberger, Peter H.1, Author              
Yin, Jian, Author
Affiliations:
1Peter H. Seeberger - Automated Systems, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863306              

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Free keywords: Covalent-organic frameworks; Chemotherapy; Interventional photodynamic therapy; Bimodal therapy; Hepatocellular carcinoma
 Abstract: Very limited treatment options are available to fight hepatocellular carcinoma (HCC), a serious global health concern with high morbidity and mortality. The integration of multiple therapies into one nanoplatform to exert synergistic therapeutic effects offers advantages over monotherapies. Here, we describe the construction of the nanoplatform Sor@GR-COF-366 for synergistic chemotherapy and photodynamic therapy (PDT) for HCC using a porphyrin-based covalent organic framework (COF-366) coated with N-acetyl-galactosamine (GalNAc) and rhodamine B (RhB), and loaded with the first-line agent, Sorafenib (Sor). The nanoplatform is targeted towards ASGPR-overexpressed HCC cells and liver tissues by GalNAc and observed by real-time imaging of RhB in vitro and in vivo. The nanoplatform Sor@GR-COF-366 exerts an enhanced synergistic tumor suppression effect in a subcutaneous HCC mouse model with a tumor inhibition rate (TGI) of 97% while significantly prolonging survival at very low toxicity. The potent synergistic therapeutic outcome is confirmed in an orthotopic mouse model of HCC with the TGI of 98% with a minimally invasive interventional PDT (IPDT). Sor@GR-COF-366 is a promising candidate to be combined with chemo-IPDT for the treatment of HCC. Statement of Significance This work describes the construction of covalent-organic frameworks (COFs) modified with glyco-moieties to serve as hepato-targeted multitherapy delivery systems. They combine minimally invasive interventional photodynamic therapy (IPDT) triggered synergism with chemotherapy treatment for hepatocellular carcinoma (HCC). With the aid of minimally invasive intervention, PDT can elicit potent anti-cancer activity for deep solid tumors. This platform shows strong therapeutic outcomes in both subcutaneous and orthotopic mouse models, which can significantly prolong survival. This work showed an effective combination of a biomedical nano-formulation with the clinical operational means in cancer treatment, which is greatly promising in clinical translation.

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Language(s): eng - English
 Dates: 2022-06-112022
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: DOI: 10.1016/j.actbio.2022.06.012
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Title: Acta Biomaterialia
  Other : Acta Biomater.
Source Genre: Journal
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Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 148 Sequence Number: - Start / End Page: 206 - 217 Identifier: ISSN: 1742-7061