2. Academic Validation
  3. Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy

Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy

  • Biomaterials. 2024 Jul:308:122550. doi: 10.1016/j.biomaterials.2024.122550.
Xiu-Hai Wu 1,  Jia-Qi Wang 2,  Man-Di Wang 3,  Ting Xiao 4,  Yu Wang 3,  Jia-Yuan Niu 5,  Lu Wang 6,  Da-Yong Hou 7,  Bo Fu 1,  Zimo Liu 8,  Hao Wang 9,  Wanhai Xu 10
Affiliations

Affiliations

  • 1 Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150081, China; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China; NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China.
  • 2 Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150081, China; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
  • 3 CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China; Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53719, USA.
  • 4 Henan Institute of Advanced Technology, Zhengzhou University, No.100 Science Avenue, Zhengzhou, 450052, China.
  • 5 CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 6 NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China.
  • 7 Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150081, China; NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China.
  • 8 CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
  • 9 CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China. Electronic address: wanghao@nanoctr.cn.
  • 10 Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150081, China; NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. Electronic address: xuwanhai@hrbmu.edu.cn.
PMID: 38581762 DOI: 10.1016/j.biomaterials.2024.122550
Abstract

Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1. The resultant fibrous glue is capable of normalizing tumoral vasculature as well as restricting immune escape. The pre-GP1 retains a 6-fold higher penetration depth than that of antibody in the multicellular spheroids (MCSs) model. It also shows remarkable tumor growth inhibition (TGI) from 19% to 61% in a murine advanced large tumor model compared to the clinical combination therapy. In addition, in the orthotopic renal tumor preclinical model, the lung metastatic nodules are reduced by 64% compared to the clinically used combination. This pre-GP1 provides a promising strategy to control the progression and metastasis of advanced renal carcinoma.

Keywords

Advanced renal carcinoma; Immunotherapy; Peptide; Self-assembly; Vascular normalization.

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