Nanotechnologies for Intracellular Protein Delivery: Recent Progress in Inorganic and Organic Nanocarriers

Abstract

From recombinant insulin to monoclonal antibodies, proteins have become essential drugs in the therapeutic arsenal and respond to a broad spectrum of diseases. While commercially available proteins have an extracellular activity, intracellular targets could be a powerful alternative to treat many pathologies such as cancers, immune disorders, but also infectious diseases. Nevertheless, to enter the cell and reach the target organelle or molecule, therapeutic proteins have to face numerous barriers (internalisation, endosomal escape, cytoplasm trafficking). In view of the fragile nature and high heterogeneity of proteins in term of size, charge and hydrophilic/lipophilic profile, the development of an efficient cytoplasm delivery system remains a long-standing challenge. The discovery of several gene editing tools (CRISPR-Cas9, TALEN, or other ZFP) has particularly boosted this research field in the last decade. Among delivery systems that can be used in vivo, some synthetic nanovectors offer interesting opportunities. In this review, we decided to describe the most recent progress in development of inorganic (silica, gold, phosphate, metal organic framework, carbon nanoparticles) as well as organic (polymer, lipid) nanoparticles both applied to intracellular protein delivery.

Intervention with the Bone-Associated Tumor Vicious Cycle through Dual-Protein Therapeutics for Treatment of Skeletal-Related Events and Bone Metastases

“…As shown in Figure 1B and Figure S2, we can see the characteristic peaks of ALN, PEG, and HA on 1 H NMR and FT-IR spectra of ALN-PEG-HA. In addition, we confirmed the characteristic peak of phosphorus existed in 31 P NMR spectra of synthesized ALN-PEG-HA (Figure 1C), which further confirmed the successful synthesis of the polymers, as phosphorus atoms resided only in the molecular structure of ALN. In addition, we also synthesized CH 3 O-PEG-HA polymers as a control (Figure S3, Figure S4, Figure S5).…”

“…In addition, proteins are hardly to be very steadily encapsulated by common polymer and liposome nanovectors with high loading capacity, due to their complex charge properties and tertiary structure . Although several drug carriers have been reported in recent years for cytosolic protein delivery in vivo , there are still huge and urgent clinical demands to develop carriers for more efficient targeting delivery of the therapeutic proteins inside cytoplasm. − Inspiringly, metal–organic frameworks (MOFs) have been developed recently as a general strategy for encapsulation and cytosolic delivery of protein cargoes under mild fabricated conditions, which is emerging as a promising drug delivery system (DDS) toward the field of protein-based therapeutics. − …”

Too advanced for assessment? Advanced materials, nanomedicine and the environment

“…There are clearly knowledge gaps concerning the environmental fate and effects and regulatory assessment of these (modified) biomolecules [ 35 ], which can be considered nanomedicines, advanced material medicinal products or constitute building blocks for such compounds. Knowledge gaps are enormous when considering the whole range of advanced therapeutic agents under development: products that act based on morphological changes like, e.g., so-called nanotransformers [ 36 ], DNA origami scissors [ 37 ] or nanocarrier systems including nanomaterials like, e.g., graphene- and CNT (carbon nanotube)-based products [ 38 ]. Information and ways to characterize and assess environmental fate and effects of such functionally novel compounds, but also for polymers and other carrier systems, or diagnostics [ 39 ] are lacking.…”

Polymeric Nanostructures Containing Proteins and Peptides for Pharmaceutical Applications

“…Regarding the complexity of therapeutic protein and peptide delivery, the field of nanotechnology has effectively bridged the gap, as it provides several nanoscale systems that have the required encapsulating properties, further offering a better pharmacokinetic profile [18,19]. Such nanosystems include lipid nanoparticles [20], liposomes [21], polymeric nanoparticles [22], and magnetic nanoparticles [23], among others.…”