Co-delivery of phagocytosis checkpoint and STING agonist by a Trojan horse nanocapsule for orthotopic glioma immunotherapy

Journal article

Rationale: Cancer immunotherapy has demonstrated significant antitumor activity in a variety of tumors; however, extensive infiltration of immunosuppressive tumor-associated macrophages (TAMs) in the glioblastoma (GBM) tumor microenvironment (TME) and the existence of the blood-brain barrier (BBB) might lead to failure of the checkpoint blockade therapy. Methods: Herein, we have developed a smart "Trojan horse" BBB-permeable nanocapsule termed "NAcp@CD47" to deliver anti-CD47 antibodies and stimulator of interferon genes (STING) agonists into GBM tissues in a stealth-like manner to reshaped the immune microenvironment by switching the phenotype of microglia and macrophages. Results: Both in vitro and in vivo studies demonstrate that NAcp@CD47 could effectively penetrate the BBB, increase the polarization of M1-phenotype TAMs, help reduce tumor immunosuppression, and inhibit the orthotopic GBM growth by phagocytosis of macrophages and microglia. Conclusions: Our findings indicate that the well-designed NAcp@CD47 not only enhances the phagocytosis of cancer cells but also efficiently enhance antitumor immunogenicity and reverses immune suppression to convert uninflamed "cold" tumors into "hot" tumors.

Authors: Zhou, Y; Guo, Y; Chen, L; Zhang, X; Wu, W

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Ivyspring International Publisher
• Journal: Theranostics
• Volume: 12
• Issue: 12
• Pages: 5488-5503
• Publication date: 2022-07-18
• DOI: 10.7150/thno.73104
• EISSN: 1838-7640
• ISSN: 1838-7640
• Language: English
• Keywords: Cancer research; Immunology; Immune system; Medicine; Inflammation; Cancer immunotherapy; Phagocytosis; Immune checkpoint; CD47; Glioma; Tumor microenvironment; Microglia; Immunotherapy