Breakable Hybrid Organosilica Nanocapsules for Protein Delivery

Abstract

The direct delivery of specific proteins to live cells promises a tremendous impact for biological and medical applications, from therapeutics to genetic engineering. However, the process mostly involves tedious techniques and often requires extensive alteration of the protein itself. Herein we report a straightforward approach to encapsulate native proteins by using breakable organosilica matrices that disintegrate upon exposure to a chemical stimulus. The biomolecule-containing capsules were tested for the intracellular delivery of highly cytotoxic proteins into C6 glioma cells. We demonstrate that the shell is broken, the release of the active proteins occurs, and therefore our hybrid architecture is a promising strategy to deliver fragile biomacromolecules into living organisms.

Synthesis of water-degradable silica nanoparticles from carbamate-containing bridged silsesquioxane precursor

“…Secondly, we used a well-established Molybdenum Blue colorimetric method to demonstrate the formation of monosilicic acid in the course of the degradation of ICPTES-Sorbitol SNPs and to quantify its amount. 47-42 The supernatants obtained as described above were treated with molybdic acid resulting in the formation of a yellow solution, which became blue upon the addition of ammonium iron sulfate. These reactions are characteristic of monosilicic acid conversion to silicomolybdate which is reduced by ammonium iron sulfate to yield Silicomolybdenum Blue complex.…”

“…For example, it has been reported that introducing disulfide (S-S) bridges within silica nanoparticles by co-condensation of tetraethyl orthosilicate (TEOS) and bis(triethoxysilylpropyl) disulfide leads to intracellular degradation of these nanoparticles when they are exposed to reducing agents such as glutathione (GSH). 31, 40-42 In our previous work 31 we have shown that development of disulfide-and tetrasulfide-containing SNPs with a controlled degradation profile promises effective drug delivery with a predetermined carrier elimination profile. In that research, we synthesized a series of redox-responsive polysulfide-based biodegradable SNPs with low polydispersity and with variations in size (average diameters of 58, 108, 124, and 332 nm), porosity, and composition (disulfide vs tetrasulfide bonds).…”

Rational Design of Nanocarriers for Intracellular Protein Delivery

“…[143,144] For example, Mou and co-workers have successfully confined HRP in the cavity of HSNs. Moreover, due to the external shell protection, the proteins encapsulated into the internal spaces could preserve the bioactivity from the enzymatic degradation.…”

“…[145] In vitro studies showed that this system could keep the enzyme stability in the presence of the denaturant and urea. [144] Recently, Yuan et al successfully designed biodegradable HSNs for RNaseA or native antibody Cetuximab intracellular delivering. Another study showed that the magnesium HSN, which was prepared using a modified classical Stöber method, displayed highly amount of hemoglobin and anticancer drugs absorption.…”

Sequence-selective encapsulation and protection of long peptides by a self-assembled FeII8L6 cubic cage

“…The direct binding of large, information-rich biomolecules, such as natural biopolymers, has thus not been achieved8, despite the applications that such binding could enable. In particular, of the many therapeutic peptides and proteins that have been discovered, only a few are in current use due to their low bioavailability and susceptibility to enzymatic degradation1516. Synthetic self-assembled capsules could mitigate these limitations by altering the solubility of peptides and protecting them from cleavage, following the example of previous successful interfaces between abiological and biological systems1718.…”