Rational Design of Nanocarriers for Intracellular Protein Delivery

Abstract

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.

PLGA protein nanocarriers with tailor-made fluorescence/MRI/PET imaging modalities

“…[1][2][3][4][5] Poly(lactic-co-glycolic acid) (PLGA) has demonstrated optimal properties for the encapsulation of a large variety of therapeutic agents and it is extensively employed in nanomedicine. 6,7 Moreover, PLGA-based nanocarriers have been used as drug delivery systems to administer proteins, 8,9 DNA 10 and anticancer drugs among others. 1,11,12 Nonetheless, despite their compositional similarities, any novel PLGA-based drug delivery system will require a thorough evaluation to address potential toxicity issues and study the pharmacokinetics and the pharmacodynamics of each specific carrier.…”

Recent advances in construction of small molecule-based fluorophore-drug conjugates

“…Last, although there are few successful fluorescent theranostic cases in clinical trials, it is believed that this field awaits innovations from collaborations of multidisciplinary researchers among synthetic chemists, bioengineers, biologists and others to offer better and more effective diagnostic and treatments [ [89] , [90] , [91] ].…”

Intracellular Labeling with Extrinsic Probes: Delivery Strategies and Applications

“…Lipid‐based nanocarriers are among the most common drug delivery nanoparticles, being made from natural or synthesized lipids, such as fatty acids and phospholipids. [ 17 ] They have been used to encapsulate probes, such as QDs. Al‐Jamal et al functionalized QDs with liposome to form cationic hybrid nanoparticles for living‐cell labeling.…”

“…[ 20,21 ] However, due to the endocytosis, it is difficult for those labels to enter the cytosol for specific targeting. To overcome the endosomal barrier, different ligands are conjugated to the surface to increase the endosomal escape, such as by cationic polymer coating, which is comprehensively reviewed by Qin et al [ 17 ] Fluorescent QD is a good example for intracellular labeling by surface modification. Medintz et al have reported different surface‐capping and bioconjugation strategies of QDs for intracellular delivery, therefore achieving specific cellular labeling.…”