Biophysics

Biotechnology

Nanoparticle

Nanotechnology

Nanocarriers

Chemistry

Materials science

Nanocapsules

Drug delivery

Biopharmaceutical

Rational design

Biochemistry

Intracellular

Biology

Advanced Materials

Protein/antibody therapeutics have exhibited the advantages of high specificity and activity even at an extremely low concentration compared to small molecule drugs. However, they are accompanied by unfavorable physicochemical properties such as fragile tertiary structure, large molecular size, and poor penetration of the membrane, and thus the clinical use of protein drugs is hindered by inefficient delivery of proteins into the host cells. To overcome the challenges associated with protein therapeutics and enhance their biopharmaceutical applications, various protein-loaded nanocarriers with desired functions, such as lipid nanocapsules, polymeric nanoparticles, inorganic nanoparticles, and peptides, are developed. In this review, the different strategies for intracellular delivery of proteins are comprehensively summarized. Their designed routes, mechanisms of action, and potential therapeutics in live cells or in vivo are discussed in detail. Furthermore, the perspective on the new generation of delivery systems toward the emerging area of protein-based therapeutics is presented as well.

Rational Design of Nanocarriers for Intracellular Protein Delivery