8 In this review, we focus on natural and synthetic protein scaffolds engineered with specific functional groups to impart non-native functions, including aiding the delivery of active molecules through targeting of malignant cells and overcoming cellular barriers. 5 Specific applications of protein nanocages for drug delivery have been discussed in a review by Molino et al. The advantage of both natural and synthetic protein scaffolds is that they can be exploited for the design of novel functional architectures. In contrast, synthetic protein scaffolds are designed de novo to mimic the properties of the natural scaffolds and carry out specific functions. 6 Natural protein scaffolds are structures that already exist in nature with intrinsic self-assembling properties, including viruses, ferritin and eukaryotic vaults. These protein sequences can be derived from both natural and non-natural amino-acid sequences that lead to self-assembly in various patterns. ![]() 6 The intricacy stems from selecting protein sequences that promote protein–protein interactions without nonspecific aggregation. The assembly of the functional building blocks to form protein nanoparticles, as observed in natural viruses, can seldom be mimicked by general nanofabrication techniques. Specific functional polypeptides can be modified to self-assemble into nanoparticles with or without caged structures with desirable nanoscale properties in terms of size and geometry. With the exception of peptide-displaying filamentous phages commonly used for nucleic acid and conjugated drug delivery in vitro and in vivo, these nanoparticles are hardly suitable for cell-targeted drug delivery. For example, bacteriophages have been used in peptide display, filamentous phages have been used as templates for nanofabrication and virus-like particles (VLPs) have been used as immunogens. 5 Viruses have been engineered to perform specific functions. Important aspects of protein nanocages such as biocompatibility, functional diversity, biological fabrication and flexibility of design by protein engineering make them powerful materials for various applications. Viruses have thus been an inspiration in developing diverse self-assembling protein nanocages from natural sources. 5 Viruses are stable structures that have the ability to withstand environmental pressures but are sensitive enough to detect signals or the change in signals in cellular environment, thereby releasing the nucleic acids they carry in the target microenvironment. They have evolved to mediate the exchange of nucleic acids between different chemical environments. 4 Viral capsids are naturally programmed for host-cell targeting and cell entry. Structural analyses of viruses show that they consist of a protein shell comprising a definite number of subunits that surrounds and protects its genome. The structure of viruses best represents the principles of protein assembly in nature. 3 The key biomedical applications involving the use of protein nanocages that we focus on in this review are therapeutics and diagnostics.Īmong myriad nature-derived nanocarriers, protein-based biological systems such as viruses have been a subject of intense study owing to their innate ability to penetrate cell membranes. The monodispersed subunits are modifiable through chemical and genetic methods. 1, 3 Examples of nature-derived nanocarriers include protein nanocages such as viruses, ferritin and many others that are formed by the self-assembly of protein subunits, resulting in a cage-like structure. ![]() 2 Nature-derived nanocarriers are potential alternatives to synthetic ones as they satisfy most of the key features, such as biocompatibility, water solubility and high cellular uptake efficiency with minimal toxicity. 1 Advances in the design and fabrication of synthetic carriers such as cationic liposomes, micelles, block copolymers, carbon nanotubes, dendrimers and inorganic nanoparticles are restricted by severe toxicity and low delivery efficiency. Smart nanosized materials with high stability, suitable pharmacokinetics and efficient cell permeability for delivering cargo molecules to target cells have been the requirements for an ideal drug delivery system.
0 Comments
Leave a Reply. |