Abstract
Attachment of nanoparticles (NPs) to the surface of carrier red blood cells (RBCs) profoundly alters their interactions with the host organism, decelerating NP clearance from the bloodstream while enabling NP transfer from the RBC surface to the vascular cells. These changes in pharmacokinetics of NPs imposed by carrier RBCs are favorable for many drug delivery purposes. On the other hand, understanding effects of NPs on the carrier RBCs is vital for successful translation of this novel drug delivery paradigm. Here, using two types of distinct nanoparticles (polystyrene (PSNP) and lysozyme-dextran nanogels (LDNG)) we assessed potential adverse and sensitizing effects of surface adsorption of NPs on mouse and human RBCs. At similar NP loadings (approx. 50 particles per RBC), adsorption of PSNPs, but not LDNGs, induces RBCs agglutination and sensitizes RBCs to damage by osmotic, mechanical and oxidative stress. PSNPs, but not LDNGs, increase RBC stiffening and surface exposure of phosphatidylserine, both known to accelerate RBC clearance in vivo. Therefore, NP properties and loading amounts have a profound impact on RBCs. Furthermore, LDNGs appear conducive to nanoparticle drug delivery using carrier RBCs.
Highlights
The attempts to coopt red blood cells (RBCs), natural carriers for many endogenous compounds, to carry drugs span several decades33–36
We have demonstrated that the adsorption of polystyrene beads (PSNP) induces negative effects on RBCs, whereas the adsorption of NPs made from soft biodegradable materials, lysozyme-dextran nanogels (LDNGs), does not induce negative effects on RBCs, strongly suggesting that NP properties directly relate to biocompatibility
The particles exhibited distinct surface charges; the zeta potential was strongly negative for PSNP and close to neutral for LDNG (33.27 ± 1.05 vs −0.42 ± 0.09 mV, respectively)
Summary
The attempts to coopt RBCs, natural carriers for many endogenous compounds, to carry drugs span several decades. #NP/RBC NA 53.5 ± 11.5 12.2 ± 5.5 44.3 ± 5.4 NA comforting in translational terms, it was reported that human RBCs are generally less fragile and more resistant to adverse effects of NPs than mouse RBCs48 This previous body of work leveraged the use of a model NP type, and the results strongly suggests that attachment of NPs to the surface of RBCs can lead to many advantages in NP drug delivery. LDNGs, composed of biodegradable components with validated in vivo use, have not been extensively investigated as a NP for cell-mediated delivery
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