NanoTRAIL‐Oncology: A Strategic Approach in Cancer Research and Therapy

Abstract

TRAIL is a member of the tumor necrosis factor superfamily that can largely trigger apoptosis in a wide variety of cancer cells, but not in normal cells. However, insufficient exposure to cancer tissues or cells and drug resistance has severely impeded the clinical application of TRAIL. Recently, nanobiotechnology has brought about a revolution in advanced drug delivery for enhanced anticancer therapy using TRAIL. With the help of materials science, immunology, genetic engineering, and protein engineering, substantial progress is made by expressing fusion proteins with TRAIL, engineering TRAIL on biological membranes, and loading TRAIL into functional nanocarriers or conjugating it onto their surfaces. Thus, the nanoparticle-based TRAIL (nanoTRAIL) opens up intriguing opportunities for efficient and safe bioapplications. In this review, the mechanisms of action and biological function of TRAIL, as well as the current status of TRAIL treatment, are comprehensively discussed. The application of functional nanotechnology combined with TRAIL in cancer therapy is also discussed.

Erufosine (ErPC3) Cationic Prodrugs as Dual Gene Delivery Reagents for Combined Antitumor Therapy

“…Therefore, to investigate the antitumor effect of the pro‐erufosine compounds as both gene delivery reagents and prodrugs of antiproliferative erufosine, a plasmid DNA encoding the tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL, also called Apo2L or TNFSF10) was selected. As a member of the tumor necrosis factor (TNF) superfamily, TRAIL can induce apoptosis in malignant tumors while sparing normal cells . In humans, TRAIL activates extrinsic apoptotic pathway after binding TRAIL death receptors (DRs), TRAIL‐R1 (DR4, TNFRSF10A) and TRAIL‐R2 (DR5, TNFRSF10B), and TRAIL decoy receptors that do not possess a functional death domain, TRAIL‐R3 (DcR1, TNFRSF10C) and TRAIL‐R4 (DcR2, TNFRSF10D).…”

Enhancing the antitumor activity of an engineered TRAIL-coated oncolytic adenovirus for treating acute myeloid leukemia

“…Another study also used TRAIL to enhance the targeted antitumor activity of nanocarriers by conjugating TRAIL onto their surfaces. 26 Our biodistribution analysis showed that zA4 showed improved tumor targeting and reduced liver enrichment in a THP-1 subcutaneous tumor-bearing model (Fig. 4a, b).…”

“…administration of Ad5-based vectors is hampered by the complex interactions between virus and host proteins, leading to hepatic tropism and immune clearance, and causing the Ad5 vector to be diverted away from the desired tumor targets. [25][26][27][28] As death receptors are expressed at higher levels on the surfaces of tumor cells than on normal cells, TRAIL has been used to target tumor cells. Pan et al 28 showed that TRAIL can be conjugated with a toxic small molecule for targeted delivery of the desired chemical to tumor cells.…”

Dual Gene Delivery Reagents From Antiproliferative Alkylphospholipids for Combined Antitumor Therapy

“…In order to investigate the potential of APL prodrugs in combined antitumor therapy, we performed gene delivery experiments with pUNO1-hTRAIL. This plasmid DNA encodes the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) superfamily (Shi et al, 2018 ). TRAIL suppresses tumor growth by a direct and specific mechanism without affecting normal tissues (Walczak et al, 1999 ; Nair et al, 2015 ).…”