TRAIL &amp; EGFR affibody dual-display on a protein nanoparticle synergistically suppresses tumor growth

Jun, Hee-Jin; Jang, Eue Soon; Kim, Hansol; Yeo, Mirae; Park, Seong Guk; Lee, Jaehyeok; Shin, Kyeong Jin; Chae, Young Chan; Kang, Sebyung; Kim, Eun‐Hee

doi:10.1016/j.jconrel.2022.07.004

Cited by 19 publications

(11 citation statements)

References 52 publications

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“…Levasseur et al used a similar approach for the LS-13 variant (forming 360-subunits structure) fused to a polyvalent antibody for targeted delivery. The versatility of lumazine synthase as a drug carrier was also confirmed with the displaying of both TRAIL (TNF-related apoptosis-inducing ligand [ 141 ]) and anti-EGFR (epidermal growth factor receptor) affibodies on the particle surface [ 142 ]. However, despite specific recognition of target cells in vitro, immunogenicity experiments showed the formation of an antibody immune response to cage proteins in vivo [ 143 ].…”

Section: Protein-based Targeting Self-assembling Nanoparticles For Bi...mentioning

confidence: 99%

Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo

et al. 2023

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Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within the composition of nanoparticles approved by the FDA for use in the clinic, which is associated with the insufficient effectiveness of the developed candidates, the difficulties of their biotechnological production, and inadequate batch-to-batch reproducibility. Targeted protein self-assembling nanoparticles circumvent this problem since proteins are encoded in DNA and the final protein product is produced in only one possible way. We believe that the combination of the endless biomedical potential of protein carriers as nanoparticles and the standardized protein purification protocols will make significant progress in “magic bullet” creation possible, bringing modern biomedicine to a new level. In this review, we are focused on the currently existing platforms for targeted self-assembling protein nanoparticles based on transferrin, lactoferrin, casein, lumazine synthase, albumin, ferritin, and encapsulin proteins, as well as on proteins from magnetosomes and virus-like particles. The applications of these self-assembling proteins for targeted delivery in vitro and in vivo are thoroughly discussed, including bioimaging applications and different therapeutic approaches, such as chemotherapy, gene delivery, and photodynamic and photothermal therapy. A critical assessment of these protein platforms’ efficacy in biomedicine is provided and possible problems associated with their further development are described.

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Section: Protein-based Targeting Self-assembling Nanoparticles For Bi...mentioning

confidence: 99%

Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo

et al. 2023

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“…One of the most recent research studies [ 113 ] aimed to overcome TRAIL resistance, which may be caused by the activation of a survival signal via the epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling pathway [ 114 ]. Unlike the aforementioned studies, which were focused mostly on a polyvalent display of multiple copies of TRAIL on the surface of protein cage nanoparticles, here, the polyvalent display of two different types of ligands was developed.…”

Section: Protein-based Systems For Nanodelivery Of Trail Pathway-targ...mentioning

confidence: 99%

“…Further, they were polyvalently displayed on the surface of the AaLS-ST using an ST/SC post-translational protein-ligation system to form AaLS/TRAIL/EGFRAfb. Each AaLS-based nanoparticle carried approximately 30 copies of TRAIL and EGFRAfb molecules in an equal ratio without altering the protein cage architecture [ 113 ]. The cytotoxic effect against EGFR-overexpressing cancer cells was improved upon dual display of TRAIL and EGFRAfb on the AaLS (AaLS/TRAIL/EGFRAfb) compared with that of AaLS/TRAIL both in vitro and in vivo.…”

Section: Protein-based Systems For Nanodelivery Of Trail Pathway-targ...mentioning

confidence: 99%

Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

2023

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The TRAIL (TNF-related apoptosis-inducing ligand) apoptotic pathway is extensively exploited in the development of targeted antitumor therapy due to TRAIL specificity towards its cognate receptors, namely death receptors DR4 and DR5. Although therapies targeting the TRAIL pathway have encountered many obstacles in attempts at clinical implementation for cancer treatment, the unique features of the TRAIL signaling pathway continue to attract the attention of researchers. Special attention is paid to the design of novel nanoscaled delivery systems, primarily aimed at increasing the valency of the ligand for improved death receptor clustering that enhances apoptotic signaling. Optionally, complex nanoformulations can allow the encapsulation of several therapeutic molecules for a combined synergistic effect, for example, chemotherapeutic agents or photosensitizers. Scaffolds for the developed nanodelivery systems are fabricated by a wide range of conventional clinically approved materials and innovative ones, including metals, carbon, lipids, polymers, nanogels, protein nanocages, virus-based nanoparticles, dendrimers, DNA origami nanostructures, and their complex combinations. Most nanotherapeutics targeting the TRAIL pathway are aimed at tumor therapy and theranostics. However, given the wide spectrum of action of TRAIL due to its natural role in immune system homeostasis, other therapeutic areas are also involved, such as liver fibrosis, rheumatoid arthritis, Alzheimer’s disease, and inflammatory diseases caused by bacterial infections. This review summarizes the recent innovative developments in the design of nanodelivery systems modified with TRAIL pathway-targeting ligands.

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“…Lipid nanoparticles embedded with recombinant human TRAIL gave rise to significant apoptosis in hepatic fibrosis. Levels of the proapoptotic proteins were highly expressed, and the anti-apoptotic protein (uPA) levels were significantly decreased by a self-made drug carrier pPB-SSL with rhTRAIL protein [117] .…”

Section: Lipid-based Nanoparticlesmentioning

confidence: 99%

Nano-TRAIL: a promising path to cancer therapy

Gampa¹

2023

Cancer Drug Resist

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Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand, also called apo-2 ligand (TRAIL/Apo-2L), is a cytokine that triggers apoptosis by binding to TRAIL-R1 (DR4) and TRAIL-R2 (DR5) death receptors. Apoptosis occurs through either the extrinsic or intrinsic pathway. The administration of recombinant human TRAIL (rhTRAIL) or TRAIL-receptor (TRAIL-R) agonists promotes apoptosis preferentially in cancerous cells over normal cells in vitro; this phenomenon has also been observed in clinical studies. The limited efficacy of rhTRAIL in clinical trials could be attributed to drug resistance, short half-life, targeted delivery issues, and off-target toxicities. Nanoparticles are excellent drug and gene delivery systems characterized by improved permeability and retention, increased stability and biocompatibility, and precision targeting. In this review, we discuss resistance mechanisms to TRAIL and methods to overcome TRAIL resistance by using nanoparticle-based formulations developed for the delivery of TRAIL peptides, TRAIL-R agonists, and TRAIL genes to cancer cells. We also discuss combinatorial approaches of chemotherapeutic drugs with TRAIL. These studies demonstrate TRAIL’s potential as an anticancer agent.

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TRAIL & EGFR affibody dual-display on a protein nanoparticle synergistically suppresses tumor growth

Cited by 19 publications

References 52 publications

Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo

Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo

Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

Nano-TRAIL: a promising path to cancer therapy

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