Remote Loading of Small‐Molecule Therapeutics into Cholesterol‐Enriched Cell‐Membrane‐Derived Vesicles

Abstract

The increasing popularity of biomimetic design principles in nanomedicine has led to therapeutic platforms with enhanced performance and biocompatibility. This includes the use of naturally derived cell membranes, which can bestow nanocarriers with cell-specific functionalities. Herein, we report on a strategy enabling efficient encapsulation of drugs via remote loading into membrane vesicles derived from red blood cells. This is accomplished by supplementing the membrane with additional cholesterol, stabilizing the nanostructure and facilitating the retention of a pH gradient. We demonstrate the loading of two model drugs: the chemotherapeutic doxorubicin and the antibiotic vancomycin. The therapeutic implications of these natural, remote-loaded nanoformulations are studied both in vitro and in vivo using animal disease models. Ultimately, this approach could be used to design new biomimetic nanoformulations with higher efficacy and improved safety profiles.

Traceable Bioinspired Nanoparticle for the Treatment of Metastatic Breast Cancer via NIR‐Trigged Intracellular Delivery of Methylene Blue and Cisplatin

“…[14b] The gelatin nanogels used here were homogenous spheres of ≈70 nm in diameter under transmission electron microscope (TEM) (Figure S1, Supporting Information), and the mice RBC‐derived RVs were hollow vesicles of ≈200 nm with negative surface charge comparable to RBC membrane (Figures S1 and S2, Supporting Information). The obtained MPVs were spherical particles under TEM, with a less stained core (≈70 nm) and a shell that was usually burst by water‐soaked core nanogel under vacuum (Figure B), which phenomenon was also observed by Zhang et al when imaging their cell‐membrane–derived vesicles . The thickness of the shell was ≈8 nm, similar to that observed from RVs and was consistent with previously reported value (7–8 nm[14a]).…”

Exosomes and Exosome-Inspired Vesicles for Targeted Drug Delivery

“…The only relevant report found was that of Zhang t al. [138] who tested the remote loading method in Red Blood cell (RBC) ghosts that were reconstructed into vesicles. It was found that the membranes needed to be enriched with cholesterol in order to retain a fluorescent dye, and up to 10% cholesterol was tested, while the fluorescence signal reached a plateau after 5% cholesterol.…”

Engineering Cell Membrane‐Based Nanotherapeutics to Target Inflammation

“…[28] Additionally, liposomes were introduced to fuse with cell membrane-derived vesicles, facilitating the encapsulation and controlled release of small molecules ( Figure 2C). [29] These drug-loaded, cholesterol-fused cell membrane vesicles were able to outperform the corresponding free drugs in both a murine model of breast cancer and a methicillin-resistant S. aureus (MRSA) skin infection model, with fewer concerns regarding safety and immunogenicity. [29] These drug-loaded, cholesterol-fused cell membrane vesicles were able to outperform the corresponding free drugs in both a murine model of breast cancer and a methicillin-resistant S. aureus (MRSA) skin infection model, with fewer concerns regarding safety and immunogenicity.…”

“…[41] Nanoparticles with a hydrazine moiety could be conjugated to the aldehyde groups to form stable secondary amine linkages through the Mannich reaction ( Figure 2F). [29] Copyright 2017, Wiley. [42] This so-called Adv.…”