Assembly of Protein Cages for Drug Delivery

Abstract

Nanoparticles (NPs) have been widely used as target delivery vehicles for therapeutic goods; however, compared with inorganic and organic nanomaterials, protein nanomaterials have better biocompatibility and can self-assemble into highly ordered cage-like structures, which are more favorable for applications in targeted drug delivery. In this review, we concentrate on the typical protein cage nanoparticles drugs encapsulation processes, such as drug fusion expression, diffusion, electrostatic contact, covalent binding, and protein cage disassembly/recombination. The usage of protein cage nanoparticles in biomedicine is also briefly discussed. These materials can be utilized to transport small molecules, peptides, siRNA, and other medications for anti-tumor, contrast, etc.

Keywords: VLPs; drug delivery; nanoparticles; protein cage.

Figure 2

The strategy of encapsulating drugs with protein cage NPs. (a) TB³⁺ diffuses into encapsulin. Reprinted with permission from Ref. [19]. Copyright 2018, American Chemical Society. (b) Positively charged green fluorescent protein GFP (+36) could be encapsulated into AfFtn. Reprinted with permission from Ref. [21]. Copyright 2021, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (c) SC/ST create a covalent isopeptide bond to encapsulate HA_head. Reprinted with permission from Ref. [32]. Copyright 2020, American Chemical Society. (d) To encapsulate HA_head, LPETG amino acid sequences and polyglycine establish a covalent connection. Reprinted with permission from Ref. [33]. Copyright 2017, American Chemical Society. (e) EGFP encapsulation into CCMV VLPs under pH control. Reprinted with permission from Ref. [34]. Copyright 2009, American Chemical Society. (f) Urea-regulated HFn disassembly/reassembly. Reprinted with permission from Ref. [35]. Copyright 2022, Informa Healthcare.

Figure 3

The strategy of drug gusion expression on SP of P22 VLPs. (a) P22 self-assembly with coat protein and cargo-scaffold-protein fusion. Reprinted with permission from Ref. [51]. Copyright 2011, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. (b) Continuous expression of P22 VLPs with three enzymes under the control of the same promoter. Reprinted with permission from Ref. [44]. Copyright 2014, American Chemical Society. (c) Two plasmids separately containing the hydrogenase cargo (hyaA-SP and hyaB-SP) and coat protein (CP) under the control of different promoters, to produce P22 capsids packed with both subunits of EcHyd-1. Reprinted with permission from Ref. [42]. Copyright 2022, American Chemical Society.

Figure 4

Application of several protein cage NPs. (a) P22 VLP-OVA capsid protein efficiently stimulated the CTL immune response in mice. Reprinted with permission from Ref. [55]. Copyright 2021, Elsevier Ltd. (b) Gd(III)-DOTA-AaLS for Nuclear Magnetic Resonance Imaging. Reprinted with permission from Ref. [26]. Copyright 2021, Elsevier B.V. (c) P22 VLPs encapsulates venom peptides and releases by ROMP disassembly strategy. Reprinted with permission from Ref. [64]. Copyright 2021, American Chemical Society. (d) Negatively charged siRNA is encapsulated by CCMV and cross-linked with DTSSP to provide stable VLPs for in vitro delivery. Reprinted with permission from Ref. [14]. Copyright 2019, American Chemical Society.

Figure 1

Several protein cages of different sizes. Fn, Ferritin cage; AaLS, Aquifex aeolicus; encapsulin protein cage; MS2; CCMV, Cowpea chlorotic mottle virus; BMV, Bromemosaic virus; P22, Bacteriophage.