Protocells: Modular Mesoporous Silica Nanoparticle‐Supported Lipid Bilayers for Drug Delivery

Abstract

Mesoporous silica nanoparticle supported-lipid bilayers, termed ‘protocells,’ represent a potentially transformative class of therapeutic and theranostic delivery vehicles. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single ‘magic bullet’. Consequently the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous silica core can have variable size and shape to direct biodistribution and controlled pore size and surface chemistry to accommodate diverse cargos. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as PEG to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. This mini-review describes the individual components of the platform, including the mesoporous silica nanoparticle core and supported lipid bilayer, their assembly (by multiple techniques) into a protocell, and the combined, often synergistic, performance of the protocell based on in vitro and in vivo studies including assessment of biocompatibility and toxicity. We close by commenting on the many emerging variations of the protocell theme and the future directions for protocell research.

A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells

“…The values obtained were ~−18 mV and ~−5.2 mV for MSNPs cores and protocells, respectively (Table 1). While a low zeta potential value is associated with electrostatic instability, zwitterionic protocells exhibit sustained size stability in PBS due to their zwitterionic surface and water hydration (Butler et al, 2016). The change in z-potential value following fusion of the supported lipid bilayer indicated successful protocell assembly.…”

Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety, Delivery Strategies, and Biomedical Applications

“…The release mechanism may be a change of the glucose concentration, or, a change of pH as involved in the lysosomes (pH 5.0–5.5) with the destabilized electrostatic BSA (p K a 4.9) coating of MSNs . Lipid‐coated MSNs were developed by Brinker and co‐workers and have the advantage to enhance the dispersibility, biocompatibility, and cellular internalization of MSNs . The cargo release occurs with the endocytosis of the NPs which favor the disruption of the lipid membrane from the MSN vectors.…”

TPGS‐Functionalized Polydopamine‐Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance

“…The current treatments for lung cancer are still limited to surgical resection, radiation therapy, and chemotherapy in clinics. However, these approaches are highly aggressive or nonspecific and frequently accompanied by serious side effects due to their conspicuous toxicity to normal cells and tissues . Recently, polymeric nanoparticles (NPs) have gained considerable attention in the biomedical field and many healthcare industries for their wide applications in diagnosis and drug delivery systems .…”