Filamentous Bacteriophage—A Powerful Carrier for Glioma Therapy

Abstract

Glioma is a life-threatening malignant tumor. Resistance to traditional treatments and tumor recurrence present major challenges in treating and managing this disease, consequently, new therapeutic strategies must be developed. Crossing the blood-brain barrier (BBB) is another challenge for most drug vectors and therapy medications. Filamentous bacteriophage can enter the brain across the BBB. Compared to traditional drug vectors, phage-based drugs offer thermodynamic stability, biocompatibility, homogeneity, high carrying capacity, self-assembly, scalability, and low toxicity. Tumor-targeting peptides from phage library and phages displaying targeting peptides are ideal drug delivery agents. This review summarized recent studies on phage-based glioma therapy and shed light on the developing therapeutics phage in the personalized treatment of glioma.

Phage Particles of Controlled Length and Genome for In Vivo Targeted Glioblastoma Imaging and Therapeutic Delivery

“…However, we began to see a precipitous drop in the transit half-life of 100 nm long ICG-CTX-M13 ϕ to approximately 100 min and a further drop to approximately 70 min with 50 nm long ICG-CTX-M13 ϕ (Figure c,d). This may be attributed to the influence of the short phage particle’s rodlike geometry, 50 nm × 5 nm, which enable greater extravasation from the vasculature and renal filtration in addition to hepatic clearance, contributing to the rapid exit from the circulation. − Filamentous phages have been studied for the delivery of various types of payload into the CNS space in preclinical mouse models of glioma . The stability, uniformity in manufacturing at relatively low costs, tunability, and genetic flexibility of phage makes it an attractive nanoplatform for the treatment of various CNS diseases. − A recent study used filamentous phage to deliver cytotoxic and suicide gene therapies systematically to human glioma brain tumors in an intracranial orthotopic xenograft mouse model of glioma without any noticeable systemic or neurological toxicities .…”

“…46−50 Filamentous phages have been studied for the delivery of various types of payload into the CNS space in preclinical mouse models of glioma. 51 The stability, uniformity in manufacturing at relatively low costs, tunability, and genetic flexibility of phage makes it an attractive nanoplatform for the treatment of various CNS diseases. 52−55 A recent study used filamentous phage to deliver cytotoxic and suicide gene therapies systematically to human glioma brain tumors in an intracranial orthotopic xenograft mouse model of glioma without any noticeable systemic or neurological toxicities.…”

Approaches for bacteriophage genome engineering

“…These approaches are being explored for the targeted delivery of drugs [100] or photosensitizers to cancer cells [101] and for the development of phage-based vaccines that display antigens from human pathogens [102], including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [103]. Importantly, the ability of phages to cross the blood-brain barrier has been explored for the delivery of small drug cargos to the brain [104].…”

Investigational Microbiological Therapy for Glioma

“…Phages are also effective carriers for glioma therapy, have a greater safety profile, do not normally proliferate in mammalian hosts [ 31 ], and can be employed to transport medications across the BBB [ 67 ]. Phage display technology involves inserting DNA sequences of exogenous peptides into phage shell protein genes so that both peptides and shell proteins are expressed on the phage surface.…”