The development of natural and designed protein nanocages for encapsulation and delivery of active compounds

Protein nanocages, usually assembled from multiple subunits in a high symmetry, are three-dimensional shell-like containers, which possess an intrinsic homogeneous chamber that is segregated from the bulk environment by protein walls. Recently, due to the superiority of protein nanocage in physicochemical property and unique structure features, the exploitation of protein cage-like nanoparticles as nano-vehicles for active compounds or drug encapsulation to improve their physicochemical properties, thermal- and photo-stability, and bioavailability have become a subject of increasing interest in multiple fields. Herein, this review presents several types of natural protein nanocages from source, structure, function to their physicochemical properties, and gives a brief introduction to the novel protein nanocage design. Then, the main strategies and techniques for molecular encapsulation within protein interior cavity have been summarized, including co-assembly strategy, reversible disassembly/reassembly method, flexible pore mediated encapsulation, diffusion/binding encapsulation, and molecule-induced assembly strategy. Last, we reviewed the practical application of natural and designed protein nanocages, especially ferritin, for small molecular compound loading, and mainly focused on the encapsulation and delivery of food bioactive compounds. Notably, novel encapsulation strategies (such as Urea-, temperature-mediated approaches) and novel designed protein nanocages are proved to be more advantageous in bioactive compounds encapsulation. Despite the progress in molecule encapsulation and delivery has been achieved, practical applications of protein nanocages still remain challenges such as low yields and high costs. Thus, further research is necessary for the exploitation and development of protein nanocages as novel nano-vehicles for food active compounds. [Display omitted] •Protein nanocages possess intrinsic inner cavity for cargo encapsulation.•Redesign and bottom-up assembly are two basic strategies toward novel nanocage.•Five approaches can be applied for cargo encapsulation within protein inner cavity.•Applications of natural and designed nanocages in food science were summarized.•Future development and challenges of protein nanocages are put forward.