Polypeptide-Based Hollow Virus-Like Particles: Preparation and Drug-Loading Property

Virus-like particles (VLPs) have attracted increasing attentions in the field of drug-delivery.The ordered surface nanostructure is one of the essential structures of the natural virus. The preparation and drug-loading property of polypeptide-based hollow VLPs with ordered surface nanostructures were investigated. Starting from poly(γ-benzyl-L-glutamate)-block-poly(ethylene glycol) (PBLG-b-PEG) block copolymers, through deprotection of the benzyl group and subsequent esterification reaction, poly(γ-benzyl-L-glutamate-co-γ-cinnamyl-L-glutamate) -block-poly(ethylene glycol) (P(BLG/CLG)-b-PEG) block copolymers were synthesized, in which the cinnamyl group was photo-cross-linkable. The photo-cross-linking process of the P(BLG/CLG)-b-PEG block copolymers was tracked by the UV-Vis spectrum. Adding water to the solution of P(BLG/CLG)-b-PEG block copolymer and PS homopolymers in THF-DMF mixture (volume ratio 1/1), spherical VLPs were self-assembled from the polymer mixtures. These VLPs contained a PS homopolymer core and P(BLG/CLG)-b-PEG block copolymer shell, and the P(BLG/CLG)-b-PEG block copolymers packed orderly forming strips on the surface. When replacing the PS homopolymers by rigid PBLG homopolymers, rod-like VLPs were obtained in which the PBLG homopolymers formed bundles and P(BLG/CLG)-b-PEG block copolymers self-assembled on the surface of the PBLG homopolymer bundles into helical nanostructures. Under UV-irradiation at λ = 254 nm, the P(BLG/CLG) blocks in the shell of both the spherical and the rod-like VLPs were cross-linked through the photodimerization of the cinnamyloxy groups. To the solution of the shell-crosslinked spherical VLPs, adding a large amount of DMF could remove the PS core-forming hollow virus-like particles (HVLPs), and the strip patterns on the surface were retained. However, for the rod-like VLPs, under similar conditions, the PBLG homopolymers in the core could not be removed. The drug-loading capacity of the spherical HVLPs was evaluated by using doxorubicin (DOX) as a model drug. It was found that DOX was successfully loaded into the HVLPs with a high relative drug-loading mass fraction (230%). Releasing studies revealed that the drugs could gradually release from the VLPs, and 72 h accumulate releasing mass fraction reached about 80%. This work provides a method to prepare polypeptide-based HVLPs with surface nanostructures, and these HVLPs could find applications for drug delivery.