Self-assembled Viral Nanoparticles as Targeted Anticancer Vehicles

Abstract

Viral nanoparticles (VNPs) comprise a variety of mammalian viruses, plant viruses, and bacteriophages, that have been adopted as building blocks and supramolecular templates in nanotechnology. VNPs demonstrate the dynamic, monodisperse, polyvalent, and symmetrical architectures which represent examples of such biological templates. These programmable scaffolds have been exploited for genetic and chemical manipulation for displaying of targeted moieties together with encapsulation of various payloads for diagnosis or therapeutic intervention. The drug delivery system based on VNPs offer diverse advantages over synthetic nanoparticles, including biocompatibility, biodegradability, water solubility, and high uptake capability. Here we summarize the recent progress of VNPs especially as targeted anticancer vehicles from the encapsulation and surface modification mechanisms, involved viruses and VNPs, to their application potentials.

Rotavirus VP6: involvement in immunogenicity, adjuvant activity, and use as a vector for heterologous peptides, drug delivery, and production of nano-biomaterials

“…( A ) Different expression systems from prokaryotic E. coli [ 2 , 72 , 126 ] to eukaryotic systems such as yeast [ 17 ], insect cell/baculovirus systems (IC-BV) [ 38 , 67 ], mammalian cells [ 38 ], HSV-1 [ 90 ], and plant cells [ 37 , 89 , 127 ] have been used successfully to produce assembled structures of VP6 tubes/VLPs. ( B ) Applications of VP6 tubes/VLPs, as vaccines (immunogenicity and protection) [ 15 , 44 , 54 , 55 , 64 – 66 , 70 , 95 , 108 ], adjuvants [ 15 , 16 , 55 , 76 – 78 , 108 – 110 ], immunological carriers [ 49 , 53 , 92 , 96 , 102 , 111 ], drug delivery tools [ 5 , 91 , 122 , 126 ], and nano-biomaterials [ 5 , 23 , 24 , 41 , 42 , 50 , 91 , 122 , 126 ] …”

“…Some examples are insertion of (i) a peptide derived from the RV VP4 protein, (ii) a 14-amino-acid peptide derived from simian paramyxovirus 5 (V5 epitope), (iii) three epitopes of poliovirus type 1, (iv) three epitopes derived from the VP4 of RV, (v) two peptides (23 and 140 amino acids) derived from the M2 and HA genes of influenza A virus, and (vi) the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (S) to the surface loops or N-terminus of VP6 [ 49 , 53 , 92 , 96 , 102 , 111 ] (iv) Drug delivery Biocompatible and biodegradable RV VP6 structured protein assemblies in the form of nanotubes/VLPs are capable of encapsulating therapeutic reagents for drug delivery and have been used successfully for treatment of diseases such as cancer. [ 5 , 91 , 122 , 126 ] (v) Nano-biomaterials The VP6 tubes/VLPs form multifunctional scaffolds that can be used to create bio-electrochemical interfaces for construction of organized metallic nano-biomaterials (silver, gold, platinum), and palladium (Pd) [ 5 , 23 , 24 , 41 , 42 , 50 , 91 , 122 , 126 ] …”

“…Besides serving as immunological carriers, RV VP6 structured protein assemblies in the form of nanotubes/VLPs are capable of encapsulating therapeutic reagents for the purpose of drug delivery (Fig. 1 B) [ 122 , 126 ]. Indeed, owing to their biocompatibility, biodegradability, and encapsulation characteristics, such viral nanoparticles are suggested to act as carriers of targeted therapeutics and anticancer vehicles [ 122 ].…”

“…Indeed, owing to their biocompatibility, biodegradability, and encapsulation characteristics, such viral nanoparticles are suggested to act as carriers of targeted therapeutics and anticancer vehicles [ 122 ]. In this context, it has been reported that self-assembled RV VP6 particles fused to the small ubiquitin modifier (SUMO) domain maintain their nanotube/VLP structure in the gastrointestinal (GI) tract when administered orally and represent a suitable biodegradable carrier [ 5 , 91 , 122 , 126 ]. These results suggest the potential application of self-assembled RV VP6 particles for drug delivery to the GI tract.…”

Pastable, Adhesive, Injectable, Nanofibrous, and Tunable (PAINT) Biphasic Hybrid Matrices as Versatile Therapeutic Carriers

“…A key strategy for amplifying the efficacy of therapeutic agents (e.g., stem cells, peptide drugs, or gene carriers) in the treatment of numerous human diseases such as cancers, injuries, and genetic disorders is guiding them locally toward target lesions. Since a majority of therapeutic agents are infused into the body as aqueous suspensions that can spread easily, off-target delivery to distal regions remains a core issue that needs to be addressed to minimize safety concerns and increase therapeutic efficacy. , Intrinsic characteristics or exterior modifications of therapeutic agents, for example, the inherent capabilities of adult stem cells to track cancer cells, the attachment of targeting moieties onto drug carriers, − or the evolution of delivery vehicles, , have been employed as crucial tools to induce specificity to target lesions and subsequently boost the efficacy of the therapeutic agents. However, the microenvironment around target lesions may become complicated due to naturally occurring events such as the infiltration of complex fluids (e.g., blood complement or abdominal dropsy), angiogenesis, fibrosis, , or immune responses, all of which can hinder the arrival of therapeutic agents to the target regardless of the affinity of the agent to the lesions.…”