Bifunctional Therapeutic Peptide Assembled Nanoparticles Exerting Improved Activities of Tumor Vessel Normalization and Immune Checkpoint Inhibition

Mohammad Taleb, Mona Atabakhshi-Kashi, Yazhou Wang, Hamideh Rezvani Alanagh, Zeinab Farhadi Sabet, Fenfen Li, Keman Cheng, Chen Li, Yingqiu Qi, Guangjun Nie, Zhao Ying

Research output: Contribution to journalArticlepeer-review

Abstract

The effectiveness of cancer immunotherapy is impaired by the dysfunctional vasculature of tumors. Created hypoxia zones and limited delivery of cytotoxic immune cells help to have immune resistance in tumor tissue. Structural and functional normalization of abnormal tumor vasculature provide vessels for more perfusion efficiency and drug delivery that result in alleviating the hypoxia in the tumor site and increasing infiltration of antitumor T cells. Taking advantage of peptide amphiphiles, herein, a novel peptide amphiphile nanoparticle composed of an antiangiogenic peptide (FSEC) and an immune checkpoint blocking peptide (DPPA) is designed and characterized. FSEC peptide is known to be involved in vessel normalization of tumors in vivo. DPPA is an inhibitory peptide of the PD-1/PD-L1 immune checkpoint pathway. The peptide amphiphile nanoparticle sets out to test whether simultaneous modulation of tumor vasculature and immune systems in the tumor microenvironment has a synergistic effect on tumor suppression. Increased intratumoral infiltration of immune cells following vascular normalization, and simultaneously blocking the immune checkpoint function of PD-L1 reactivates effective immune responses to the tumors. In summary, the current study provides a new perspective on the regulation of tumor vessel normalization and immunotherapy based on functional peptide nanoparticles as nanomedicine for improved therapeutic purposes.

Original languageEnglish (US)
Article number2100051
JournalAdvanced Healthcare Materials
Volume10
Issue number12
DOIs
StatePublished - Jun 23 2021

Keywords

  • combination therapy
  • immune checkpoint inhibitors
  • peptide amphiphile
  • peptide nanoparticles
  • vessel normalization

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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