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.

Keywords: Filamentous phage; drug delivery; nanoparticles; phage display; targeting.

Figure 1.

General concept of using phage for drug and gene delivery. (A) Identification of target-recognizing peptide through bio-screening. A phage library is mixed with immobilized targets and incubated for a proper time. Unbound phages are then washed away with a washing buffer. Bound phages are eluted with an elution buffer, and amplified using medium containing preincubated E.coli bacteria and then acted as a new input library for next round bio-screening. After 3 ∼ 5 rounds, the selected phage clones are identified. (B) The paradigm of drug and gene delivery using phage particles. Phage can be chemically modified and/or genetically engineered to load drugs (a) and carry foreign genes (b), respectively. Phage can also be incorporated with other nanometer carriers for drug and gene delivery, such as liposomes (c) and nanoparticles (d). (C) The paradigm of drug and gene delivery using phage-borne proteins. Wild type or fused phage proteins can be inserted into liposomes (e) and polymer nanoparticles (g) to form phage-mimetic complexes, and even self-assembly into nanophage (f) to deliver drug and gene.