Red Blood Cells-Derived Vesicles for Delivery of Lipophilic Drug Camptothecin

Abstract

Recently, cell membrane-derived nanoparticles, particularly of RBCs, have been explored for delivery of hydrophilic solutes of varied size and complexities. So far, these naturally derived nanoparticles show a significant overlap with liposomes in terms of stability, solute encapsulation, and release. Unlike hydrophilic molecules, which are loaded inside the aqueous core, hydrophobic moieties largely partition inside the lipophilic shell, hence fate of these nanocarriers may be different. Since vesicles have more complex membrane architecture (due to natural lipids and additional proteins and glycoproteins), ease of loading hydrophobic drug, its release pattern, and overall particle stability cannot be compared to those of synthetic lipid-based carriers. Therefore, we derived nanovesicles (NVEs) from RBC membrane, loaded with hydrophobic drug camptothecin (CPT) and labeled noncovalently with amphiphilic fluorophore (CM-DiI). Although both CPT and CM-DiI are known to partition inside the membrane, the overall stability of NVEs and composition of membrane proteins, particularly CD47, "marker of self", did not change. Additionally, the developed NVEs were found to be nonphagocytic even in the presence of serum and showed minimal stimulation of macrophages to release cytokines. Further, this system showed slow release but strong retention of CPT and CM-DiI, respectively, over 24 h, hence appropriate for theranostic applications. Also, NVEs were internalized by lung carcinoma cells and possessed slightly higher toxicity than free CPT. When injected intravenously in balb/c mice, these nanovesicles showed higher retention in blood over 48 h and insignificant accumulation in vital organs like heart and kidneys, thus suggesting its potential for in vivo application. We believe that this system has superior stealth and comparable physicochemical properties to synthetic lipid-based nanocarriers; hence, it can be further developed as personalized medicine.

Coincident Fluorescence‐Burst Analysis of the Loading Yields of Exosome‐Mimetic Nanovesicles with Fluorescently‐Labeled Cargo Molecules

“…[22][23][24] Among them, approaches for the production and loading of nanovesicles from detergent-resistant membranes (DRM) of red blood cells (RBC) are particularly promising, for the perspective scalability of their production and loading processes. [25,26] All potential applications of exosomes and exosome-mimetic nanovesicles for therapeutic drug delivery call for the development of suitable experimental and analysis techniques to accurately quantify their loading. [27][28][29][30][31] Key challenges in this respect arise from the very small sizes (30-150 nm in diameter) and the wide heterogeneity of natural exosomes and of their biomimetic counterparts.…”

Bioinspired by cell membranes: functional polymeric materials for biomedical applications

“…2). 67 In another work, Dong et al derived nanovesicles from neutrophils and loaded them with Resolvin D2 (RvD2-HVs) for brain damage recovery during an ischemic stroke. These RvD2-HVs have a hydrodynamic diameter and zeta potential of B200 nm and À14 mV, respectively.…”

Cells-Based Drug Delivery for Cancer Applications

“…The diameter of NPs used in the studies is similar to that of bacteria, viruses and other pathogens, generally about 100 nm, so the clearance mechanism of reticuloendothelial system in vivo is easy to be activated. Cell-derived NPs reduce the stimulation of macrophages to release cytokines greatly [ 60 ]. A serious problem of NPs is that they will come into contact with plasma proteins when they enter the blood system.…”