Promises and Pitfalls of Intracellular Delivery of Proteins

Abstract

The direct delivery of functional proteins into the cell cytosol is a key issue for protein therapy, with many current strategies resulting in endosomal entrapment. Protein delivery to the cytosol is challenging due to the high molecular weight and the polarity of therapeutic proteins. Here we review strategies for the delivery of proteins into cells, including cell-penetrating peptides, virus-like particles, supercharged proteins, nanocarriers, polymers, and nanoparticle-stabilized nanocapsules. The advantages and disadvantages of these approaches including cytosolar delivery are compared and contrasted, with promising pathways forward identified.

Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles

“…The transient nature of therapeutic protein delivery makes it an attractive method for delivery of genome-editing proteins (4). A challenge to efficient delivery of genome-editing proteins is their proteolytic instability and poor membrane permeability (6). Developing delivery vehicles to transport active protein to their intracellular target site is thus essential to advance protein-based genome editing.…”

“…The last few years have witnessed tremendous progress in designing nanocarriers for intracellular protein delivery (7,8). However, the lack of an effective, general approach to load protein into a stable nanocomplex and the inefficient release of protein from endocytosed nanoparticles pose challenges for protein delivery (6). There remains a great demand for the development of novel platforms that efficiently assemble protein into nanoparticles for intracellular delivery while maintaining biological activity of the protein.…”

A Photoactive Carbon‐Monoxide‐Releasing Protein Cage for Dose‐Regulated Delivery in Living Cells

“…[4][5][6][7] These composites,w hich have large numbers of metal compounds appropriately aligned on or within the scaffolds,s how ah igh reactivity when externally stimulated, for example,b yl ight irradiation. [8][9][10] Protein assemblies containing metal compounds are biocompatible and have been recently used for both in vitro and in vivo applications.…”

Biodegradable double nanocapsule as a novel multifunctional carrier for drug delivery and cell imaging

“…1 Although nanoformulation provides an interesting approach to the direct delivery of proteins, 2,3 the use of biodegradable nanocapsules still holds great promise because of their remarkable superiority in cell transduction efficiency and biocompatibility. 4 Besides the delivery of proteins into cells, real-time and noninvasive assessment of delivery efficiency and therapeutic response is another important task, and the assessment requires concomitant delivery of imaging agents in one capsule, not only to trace the transduction process but also to measure cell response.…”