Red blood cells: a potential delivery system

Abstract

Red blood cells (RBCs) are the most abundant cells in the body, possessing unique biological and physical properties. RBCs have demonstrated outstanding potential as delivery vehicles due to their low immunogenicity, long-circulating cycle, and immune characteristics, exhibiting delivery abilities. There have been several developments in understanding the delivery system of RBCs and their derivatives, and they have been applied in various aspects of biomedicine. This article compared the various physiological and physical characteristics of RBCs, analyzed their potential advantages in delivery systems, and summarized their existing practices in biomedicine. Graphical Abstract

Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

“…Biological DDS are based on natural cells and their derivatives (e.g., RBC ghosts and EVs) and have the significant advantage of biocompatibility. RBCs have been examined as drug carriers since the 1970s and are felt to be useful for this purpose due to their long circulation lifespan, which ensures sustained drug release over time, and their lack of a nucleus and organelles, which provide “space” for drugs ( Chen et al, 2023 ). They can encapsulate therapeutic molecules or carry them on their surface.…”

“…However, some factors need to be considered before extensive applications in clinical settings. Indeed, during the process of producing RBC-based drug delivery systems, RBCs become less deformable, while the change in the viscoelasticity of their cytoplasm affects cell dynamics ( Chen et al, 2023 ). A decrease in deformability is also observed during surface coupling of therapeutic molecules to the RBC membrane, along with loss of CD47 (integrin-associated protein) and externalization of phosphatidylserine ( Villa et al, 2016 ), all of which can act as signals for rapid clearance from the circulation ( Burger et al, 2012 ; Nguyen et al, 2011 ; Sosale et al, 2015 ).…”

“…Taken together, these underline the need for strict control of the mechanical properties of RBCs modified for drug transport to extend their circulation time after administration. The pros and cons of using RBCs or their cellular derivatives as drug carriers exceed the scope of the present work and are extensively reviewed elsewhere ( Chen et al, 2023 ; Tzounakas et al, 2017 ; Villa et al, 2016 ). Nonetheless, we believe that RBCs will remain a focus of drug delivery innovation.…”

Drug-loaded erythrocytes: Modern approaches for advanced drug delivery for clinical use

“…Presently, alongside the achievements in targeted drug delivery achieved through encapsulation within RBCs, there exists a broad spectrum of innovative technologies. These encompass RBC membrane-camouflaged nanoparticles (RCNPs), red blood cell-derived extracellular vesicles (RBCEVs), and the concept of RBC-Hitchhiking [ [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] ].…”

“…Alongside the achievements in targeted drug delivery achieved through encapsulation within RBCs, a wide array of innovative technologies exists, including RBC membrane-camouflaged nanoparticles, RBC-derived extracellular vesicles and RBC-Hitchhiking. Most of these review articles summarize mainly preclinical studies conducted in vitro or using animal models [ [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] ].…”