Intracellular protein delivery by hollow mesoporous silica capsules with a large surface hole

Abstract

We prepared cell membrane-permeable hollow mesoporous silica capsules (HMSCs) by a simple new method. CTAB micellar assembly in cholesterol emulsion gave rise to a novel capsular morphology of the HMSC particles. The HMSCs consisted of mesostructured silica walls with a large surface hole (25-50 nm) and the average particle dimension was 100-300 nm. They exhibited high surface areas of up to 719.3 m(2) g(-1) and a mesoporous range of pores of 2.4-2.7 nm. The surface-functionalized HMSCs could also be prepared by a similar co-condensation method using tetraethoxysilane with various organoalkoxysilane precursors in the presence of cholesterol. These organically modified HMSCs could be further modified on demand. For example, a carboxy-functionalized HMSC could be surface-functionalized by a green fluorescent 5-aminofluorescein (AFL) through an amidation reaction to afford a fluorescent AFL-HMSC. The hollow capsular morphology of the HMSCs with a large surface hole enabled us to develop very efficient intracellular delivery systems for membrane-impermeable ions, molecules, and various functional proteins. Non-covalent sequestration and delivery of proteins as well as covalent linkage of fluorescent molecules on the silica surface are effective for this system. The highly negatively charged green fluorescent probe mag-fluo-4 could be intracellularly delivered into HeLa cells by HMSC without any difficulty. The HMSCs could also effectively transport large functional proteins such as antibodies into HeLa cells. The efficiency of protein delivery by HMSC seems to be 3-22-fold higher than that of mesoporous silica nanospheres (MSNs) based on confocal laser scanning microscopy (CLSM) analysis.

Nanoparticle Vaccines Against Infectious Diseases

“…Nano-immuno stimulators are the nano scale (20–100 nm) vaccine particles that can improve the vaccine efficacy in vivo better than bulk molecules ( 20 , 29 ). Some of the known nano-immuno stimulators that have been used for this specific purpose are inorganic NPs (iron and silica) ( 30 , 31 ), polymeric NPs (chitosan, PLGA, PVPONAlk, γ-PGA) ( 32 – 37 ), liposomes (cholesterol and lipids) ( 33 , 38 ) and virus like particles (VLPs) ( 39 , 40 ). Different types of NPs used to deliver antigens to give protection against different diseases have been listed in Table 1 .…”

“…Of note the size of NPs was also found to influence the activation of signaling pathways. A study has demonstrated that smaller NPs are able to alter the cell signaling processes more efficaciously than the large NPs ( 31 ).…”

Stimuli-responsive nanomaterials for therapeutic protein delivery

“…iii) It has been previously proved that MSNs are capable of escaping endolysosomal entrapment. MSNs functionalized with hydrophobic or acid labile moieties were recently employed to transport proteins into cells [37]. Wu et al prepared aldehyde-displaying silica nanoparticles (MSN-aldehyde) containing lysosome activatable rhodamine-lactams for controlled protein delivery via lysosomal acidity-triggered release [38].…”

Fe3O4‐Nanoparticle‐Embedded Multifunctional Hollow Mesoporous Silica Capsules

“…Most of the particles, however, have a size range of 150–300 nm and the hole size ranges from 25 to 50 nm. These dimensions are quite comparable to those of pure siliceous HMSC 8a. This large surface hole allows the inner hollow space to encapsulate cargo, which gives advantages in various applications such as protein delivery.…”

“…Therefore, the Fe 3 O 4 NPs can effectively surround the CTAB micellar assembly, and they can be uniformly embedded in the silica wall during the formation of Mag‐HMSCs. The preparation of magnetic capsular materials has been achieved by our recent method, a cholesterol‐assisted emulsion technique, in which the cholesterol molecules form an emulsion during the formation of mesostructured porous silica materials in the presence of the mesopore‐directing template, CTAB 8a. Template‐free Mag‐HMSC materials were obtained by calcination of the as‐prepared Mag‐HMSCs in air at 550 °C for 5 h. The particle morphology of Mag‐HMSCs did not significantly change during heat treatment.…”