Critical Features for Mesoporous Silica Nanoparticles Encapsulated into Erythrocytes

Abstract

Mesoporous silica nanoparticles (MSNs) hold great potential as a versatile platform for biomedical applications, especially drug delivery. However, evidence shows that MSNs even when PEGylated are rapidly cleared from the bloodstream by the monocyte phagocytic system. Erythrocytes, also called red blood cells (RBCs), can serve as biocompatible carriers of various bioactive substances, including drugs, enzymes, and peptides. In this work, we synthesize a series of fluorescent PEGylated MSNs with different synthetic diameters ranging from 10 to 200 nm and investigate the size effect on their encapsulation in human RBCs (hRBCs) by a hypotonic dialysis-based method. According to fluorescence images and flow cytometry analyses, we demonstrated that a hydrodynamic diameter below 30 nm is critical for efficient MSN encapsulation. Confocal microscopy and scanning electron microscopy images further confirmed that PEGylated MSNs were successfully embedded inside RBC. PEGylation serves an important role not only for stabilizing MSNs in biological milieu but also for reducing significant hemolysis caused by bare MSNs and thus for successful encapsulation. In addition to PEGylation, we further introduce positively charged functional groups onto the MSNs to show that nanoparticle-encapsulated hRBCs could serve as depots for delivering biological molecules through electrostatic attraction or chemical conjugation with MSNs. Also, we verify the existence of CD47 membrane protein, a marker of self, on the nanoparticle-encapsulated hRBCs and assess its ability of circulation in the blood, which could act as a circulation reservoir for delivering pharmacological substances through an osmosis-based method with MSNs.

Phototheranostics Using Erythrocyte-Based Particles

“…While most light-based RBC-derived constructs use the RBC membrane as a substrate coating, there are a growing number of constructs that use the RBC as a carrier. Constructs that use the RBC as a carrier can have a variety of optical cargos, including organic molecules [50][51][52] and NPs made from various metals [18] or semiconductors [53,54]. While constructs that use the RBC membrane as a coating primarily use sonication Constructs that employ RBC membranes as a substrate coating have also been shown to be stable, with many constructs showing minimal changes in size after storage of up to one week [42,43].…”

A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy

“…After modification with HA-conjugated dioleoyl phosphoethanolamine (HA-DOPE), the particle size increased to 220 nm (Additional file 1 : Figure S1A). The increase in the negative charge of RBCm-LCNPs relative to non-coated LCNPs improved nanoparticle stability in the blood [ 28 , 29 ]. LCNPs appeared round, showed uniform morphology and distribution, and were non-adhesive.…”

Relationship and improvement strategies between drug nanocarrier characteristics and hemocompatibility: What can we learn from the literature

“…Chen found that hemolytic activity of unmodified MSNs was higher than PEGylated MSN. This result indicated that PEGylation played an important role not only in enhancing the stability of MSNs but also in reducing significant hemolysis [129] . Liu 's study showed that RBC treated by PEG-MSNs had no visible hemolysis, and their hemolysis value was nearly 20 times lower than unmodified MSNs.…”