Control over Silica Particle Growth and Particle–Biomolecule Interactions Facilitates Silica Encapsulation of Mammalian Cells with Thickness Control

Abstract

Over the last twenty years, many strategies utilizing sol-gel chemistry to integrate biological cells into silica-based materials have been reported. One such strategy, Sol-Generating Chemical Vapor into Liquid (SG-CViL) deposition, shows promise as an efficient encapsulation technique due to the ability to vary the silica encapsulation morphology obtained by this process through variation of SG-CViL reaction conditions. In this report, we develop SG-CViL as a tunable, multi-purpose silica encapsulation strategy by investigating the mechanisms governing both silica particle generation and subsequent interaction with phospholipid assemblies (liposomes and living cells). Using Dynamic Light Scattering (DLS) measurements, linear and exponential silica particle growth dynamics were observed which were dependent on deposition buffer ion constituents and ion concentration. Silica particle growth followed a cluster-cluster growth mechanism at acidic pH, and a monomer-cluster growth mechanism at neutral to basic pH. Increasing silica sol aging temperature resulted in higher rates of particle growth and larger particles. DLS measurements employing PEG coated liposomes and cationic liposomes, serving as model phospholipid assemblies, revealed electrostatic interactions promote more stable liposome-silica interactions than hydrogen bonding and facilitate silica coating on suspension cells. However, continued silica reactivity leads to aggregation of silica coated suspensions cells, revealing the need for cell isolation to tune deposited silica thickness. Utilizing these mechanistic study insights, silica was deposited onto adherent HeLa cells under biocompatible conditions with micron scale control over silica thickness, minimal cell manipulation steps, and retained cell viability over several days.

Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization

“…By varying the buffer ionic constituents, concentration, pH, and sol aging temperature, the silica particle size in silica sols can be controlled. Reproduced from [ 145 ]. Copyright: 2017, American Chemical Society ( C ) TEM image of helical silica.…”

“…Vavia et al Furthermore, various deposition methods and liposome templates have been developed to regulate silicon shell synthesis more precisely and diversely. Tartis et al [145] used liposomes as organic templates and adopted the Sol-Generating Chemical Vapor into Liq-uid (SG-CViL) deposition strategy to control the deposition of silica (Figure 6B). The growth of silica particles was influenced by the composition and concentration of the deposition buffer ions.…”

Phospholipid prodrug conjugates of insoluble chemotherapeutic agents for ultrasound targeted drug delivery

“…Tetramethylorthosilicate (TMOS) was deposited for 15 min onto a 20 mol% 2T-N liposome sample creating silica coated vehicles using the Sol-Generating Chemical Vapor into Liquid deposition method discussed in Johnston 2017 [38]. A drop of silica-coated liposomes was absorbed onto a holey carbon coated 200-mesh copper grid and excess was removed using filter paper.…”