13 - Engineered protein and protein-polysaccharide cages for drug delivery and therapeutic applications

Abstract

Protein and protein-polysaccharide cages (PPCs) have emerged as a promising tool for drug delivery in the last few years. The primary criterion of selecting protein as a carrier is its biocompatibility, which ensures safe delivery of its cargo without eliciting adverse immunogenic response. Second, due to its properties such as unique sequences, secondary and tertiary structures, folding, clustering, domain-to-domain interactions, entangling between its chains with ionic, covalent, van der Waals, or hydrogen bonding interactions, and casting bridges between its multimers, protein leverages a unique display of cage-like structures that could be used as host to accommodate guest drug molecules with improved stability. Also, PPCs have evolved as unique nanohybrids that allow novel interactions with guest molecules and wrap them with firm interactions vis-à-vis binding forces. When attributed to such kind of payloads, protein cages (PCs) and PPC could be exploited to deliver small to macromolecular drug molecules, control their release inside body, and deliver them in either stimuli-responsive or target-specific manner. These cages may further be engineered by metal-guided intra or intermeric cross-linking, metal lacing, chemical-guided disulfide or amide bridge formation, ligand-guided epitope appending, or aptamer-tagged target furnishing. Such kind of engineering could be employed to shape the PC for improving cage stability, cavity architecture, target specificity, cellular uptake, and release property. In this chapter, we have presented all traditional PCs, their architectures, release properties, engineering approaches, and their biomedical applications. In addition, comparatively newer engineering approaches such as posttranslational modification of proteins to tune their in vivo properties have also been discussed. The perturbations of PPC in drug delivery and therapeutic applications have also been reviewed. It is noteworthy that various engineering approaches such as electrostatic complexation, chemical coupling, and electrospinning have been exploited in contemporary ages to engineer PPCs for improving their intracellular uptakes, loading capacity, in vivo drug release as well as stability. A succinct and magnanimous highlight of all these manipulations has been a major chord in this chapter, especially focusing their applications in recent days of biomedical world.