Proteins have sparked fast growing interest as biological therapeutic agents for several diseases. Antibodies, in particular, carry an enormous potential as drugs owing to their remarkable target specificity and low immunogenicity. Although the market has numerous antibodies directed towards extracellular targets, their use in targeting therapeutically important intracellular targets is limited by their inability to cross cellular membrane. Realizing the potential for antibody therapy in disease treatment, progress has been made in the development of methods to deliver antibodies intracellularly. In this review, we address various platforms for delivery of antibodies, their merits and drawbacks.
Intracellular
delivery of functional proteins is a promising, but
challenging, strategy for many therapeutic applications. Here, we
report a new methodology that overcomes drawbacks of traditional mesoporous
silica (MSi) particles for protein delivery. We hypothesize that engineering
enhancement in interactions between proteins and delivery vehicles
can facilitate efficient encapsulation and intracellular delivery.
In this strategy, surface lysines in proteins were modified with a
self-immolative linker containing a terminal boronic acid for stimulus-induced
reversibility in functionalization. The boronic acid moiety serves
to efficiently interact with amine-functionalized MSi through dative
and electrostatic interactions. We show that proteins of different
sizes and isoelectric points can be quantitatively encapsulated into
MSi, even at low protein concentrations. We also show that the proteins
can be efficiently delivered into cells with retention of activity.
Utility of this approach is further demonstrated with gene editing
in cells, through the delivery of a CRISPR/Cas9 complex.
Lysozyme, an antibacterial enzyme, was used as a stabilizing ligand for the synthesis of fairly uniform silver nanoparticles adopting various strategies. The synthesized particles were characterized using UV-visible spectroscopy, FTIR, dynamic light scattering (DLS), and TEM to observe their morphology and surface chemistry. The silver nanoparticles were evaluated for their antimicrobial activity against several bacterial species and various bacterial strains within the same species. The cationic silver nanoparticles were found to be more effective against Pseudomonas aeruginosa 3 compared to other bacterial species/strains investigated. Some of the bacterial strains of the same species showed variable antibacterial activity. The difference in antimicrobial activity of these particles has led to the conclusion that antimicrobial products formed from silver nanoparticles may not be equally effective against all the bacteria. This difference in the antibacterial activity of silver nanoparticles for different bacterial strains from the same species may be due to the genome islands that are acquired through horizontal gene transfer (HGT). These genome islands are expected to possess some genes that may encode enzymes to resist the antimicrobial activity of silver nanoparticles. These silver nanoparticles may thus also be used to differentiate some bacterial strains within the same species due to variable silver resistance of these variants, which may not possible by simple biochemical tests.
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