Drug delivery vectors based on filamentous bacteriophages and phage-mimetic nanoparticles

Abstract

With the development of nanomedicine, a mass of nanocarriers have been exploited and utilized for targeted drug delivery, including liposomes, polymers, nanoparticles, viruses, and stem cells. Due to huge surface bearing capacity and flexible genetic engineering property, filamentous bacteriophage and phage-mimetic nanoparticles are attracting more and more attentions. As a rod-like bio-nanofiber without tropism to mammalian cells, filamentous phage can be easily loaded with drugs and directly delivered to the lesion location. In particular, chemical drugs can be conjugated on phage surface by chemical modification, and gene drugs can also be inserted into the genome of phage by recombinant DNA technology. Meanwhile, specific peptides/proteins displayed on the phage surface are able to conjugate with nanoparticles which will endow them specific-targeting and huge drug-loading capacity. Additionally, phage peptides/proteins can directly self-assemble into phage-mimetic nanoparticles which may be applied for self-navigating drug delivery nanovehicles. In this review, we summarize the production of phage particles, the identification of targeting peptides, and the recent applications of filamentous bacteriophages as well as their protein/peptide for targeting drug delivery in vitro and in vivo. The improvement of our understanding of filamentous bacteriophage and phage-mimetic nanoparticles will supply new tools for biotechnological approaches.

Pf Bacteriophage and Their Impact on Pseudomonas Virulence, Mammalian Immunity, and Chronic Infections

“…Inoviruses like Pf are among the better characterized bacteriophages due to their extensive use in research and industry. Inoviruses are amenable to genetic manipulation and some species, such as M13 (Escherichia coli) are widely used in biotechnological applications, such as phage display (56) and as drug carriers (57). Pf phages are also a model system for studying the molecular mechanisms of nucleoprotein assembly and membrane transport (58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68).…”

Bacteriophages for Chronic Wound Treatment: From Traditional to Novel Delivery Systems

“…Increases in phage titers and rates of infection resolution and wound healing occurred more rapidly when compared to the non-encapsulated free phage cocktail. These FDA approved liposomes have some disadvantages, such as degrading quickly in vivo, and their large size can affect their penetration and diffusion [176].…”

Application of Bacteriophages in Nanotechnology

“…Displaying specific peptides targeting eukaryotic cells or tissues compensates for the lack of natural mechanisms to enter mammalian cells or reach appropriate intracellular compartments. Non-modified phages are sometimes used, but the efficiency of virions containing cell-specific targeting peptides developed by phage display [ 51 ] or even phage-inspired nano-carriers [ 52 ] is superior. There is a possibility of coupling a variety of loads (e.g., drugs) by genetic manipulation [ 53 , 54 ] or chemical conjugation [ 55 , 56 ].…”

“…Phage proteins themselves can also assemble into nano-carriers for gene delivery [ 52 ]. For instance, the Petrenko group showed the encapsulation of siRNA by fused protein composed of phage capsid protein and targeting moiety [ 63 ].…”