Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications

Hadad, Elad; Rudnick-Glick, Safra; Itzhaki, Ella; Avivi, Matan Y.; Grinberg, Igor; Elias, Yuval; Margel, Shlomo

doi:10.3390/polym12122996

Cited by 8 publications

(17 citation statements)

References 51 publications

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“…When a single dose of the RGD-TRAIL-ELP nanoparticle was administered intraperitoneally, the COLO-205 tumor xenograft model showed nearly total tumor shrinkage. Protein electrophoresis revealed a 3.4-fold increase in the RGD-TRAIL-ELP trimer content than RGD-TRAIL [126] . P(RGD) proteinoids (where RGD is a tripeptide) comprising arginine, glycine, and aspartic acid, and proteinoid nanocapsules (NCs) were synthesized for targeted tumor therapy.…”

Section: Polymer-based Nanoparticlesmentioning

confidence: 92%

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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Section: Polymer-based Nanoparticlesmentioning

confidence: 92%

Nano-TRAIL: a promising path to cancer therapy

Gampa¹

2023

Cancer Drug Resist

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“…Similarly, proteinoid nanocapsules have been engineered for TRAIL delivery [ 110 ]. Proteinoids are non-toxic biodegradable polymers prepared by the thermal step-growth polymerization of amino acids.…”

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

confidence: 99%

“…The RGD sequence was intended to provide additional tumor targeting due to specific binding to the αvβ3 integrin, which is widely expressed on tumor cells and tumor vessels [ 112 ]. TRAIL-P(RGD) exhibited high cytotoxicity in human ovarian cancer cells while retaining the efficiency of free TRAIL [ 110 ]. Thus, proteinoid nanocapsules potentially offer increased stability for the TRAIL ligand; however, additional in vivo studies are required.…”

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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“…Suitable molecules can be encapsulated within the internal core of the formed particle owing to hydrophobic residues; a marker (e.g., a fluorescent label) can be conjugated to the surface using hydrophilic residues such as amines [ 20 ]. Previous studies presented the encapsulation of various molecules for cosmetics (retinoic acid [ 21 ]), chemotherapeutics (doxorubicin and Paclitaxel [ 18 , 22 , 23 ], cannabidiol [ 24 ]), antipsychotics (Risperidone [ 25 ]) and dyes for diagnostic imaging (ICG [ 26 , 27 ]).…”

Section: Introductionmentioning

confidence: 99%

“…Suitable molecules can be encapsulated within the internal core of the formed particle owing to hydrophobic residues; a marker (e.g., a fluorescent label) can be conjugated to the surface using hydrophilic residues such as amines [20]. Previous studies presented the encapsulation of various molecules for cosmetics (retinoic acid [21]), chemotherapeutics (doxorubicin and Paclitaxel [18,22,23], cannabidiol [24]), antipsychotics (Risperidone [25]) and dyes for diagnostic imaging (ICG [26,27]). D-arginine (R), glycine (G) and L-aspartic acid (D) were used for randomly achieving the RGD sequence within the proteinoid backbone; previous studies showed that 13% of the established proteinoids contain the RGD sequence [26,28].…”

Section: Introductionmentioning

confidence: 99%

Tumor-Targeted Fluorescent Proteinoid Nanocapsules Encapsulating Synergistic Drugs for Personalized Cancer Therapy

et al. 2021

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Personalized cancer treatment based on specific mutations offers targeted therapy and is preferred over “standard” chemotherapy. Proteinoid polymers produced by thermal step-growth polymerization of amino acids may form nanocapsules (NCs) that encapsulate drugs overcoming miscibility problems and allowing passive targeted delivery with reduced side effects. The arginine-glycine-glutamic acid (RGD) sequence is known for its preferential attraction to αvβ3 integrin, which is highly expressed on neovascular endothelial cells that support tumor growth. Here, tumor-targeted RGD-based proteinoid NCs entrapping a synergistic combination of Palbociclib (Pal) and Alpelisib (Alp) were synthesized by self-assembly to induce the reduction of tumor cell growth in different types of cancers. The diameters of the hollow and drug encapsulating poly(RGD) NCs were 34 ± 5 and 22 ± 3 nm, respectively; thereby, their drug targeted efficiency is due to both passive and active targeting. The encapsulation yield of Pal and Alp was 70 and 90%, respectively. In vitro experiments with A549, MCF7 and HCT116 human cancer cells demonstrate a synergistic effect of Pal and Alp, controlled release and dose dependence. Preliminary results in a 3D tumor spheroid model with cells derived from patient-derived xenografts of colon cancer illustrate disassembly of spheroids, indicating that the NCs have therapeutic potential.

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Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications

Cited by 8 publications

References 51 publications

Nano-TRAIL: a promising path to cancer therapy

Nano-TRAIL: a promising path to cancer therapy

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

Tumor-Targeted Fluorescent Proteinoid Nanocapsules Encapsulating Synergistic Drugs for Personalized Cancer Therapy

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