Erythrocyte-derived nano-probes functionalized with antibodies for targeted near infrared fluorescence imaging of cancer cells

Abstract

Constructs derived from mammalian cells are emerging as a new generation of nano-scale platforms for clinical imaging applications. Herein, we report successful engineering of hybrid nano-structures composed of erythrocyte-derived membranes doped with FDA-approved near infrared (NIR) chromophore, indocyanine green (ICG), and surfacefunctionalized with antibodies to achieve molecular targeting. We demonstrate that these constructs can be used for targeted imaging of cancer cells in vitro. These erythrocyte-derived optical nano-probes may provide a potential platform for clinical translation, and enable molecular imaging of cancer biomarkers.

Optical properties of biomimetic probes engineered from erythrocytes

“…Further molecular specificity of NETs can be achieved by functionalizing their surface with appropriate targeting moieties such as antibodies [48]. …”

“…A key advantage of erythrocyte-derived constructs as compared to liposomal particles is that the former can potentially have extended circulation time due to preserved membrane proteins that prevent phagocytosis by immune cells. In a previous study [48], we demonstrated that CD47, a membrane glycoprotein, which impedes phagocytosis [38,39], remains on the surface of NETs. Other investigators have reported that polymeric nano-constructs, coated with erythrocyte-derived membranes, were retained in mice blood for three days with circulation half-life of nearly 40 hours [49].…”

Erythrocyte‐Derived Nanoparticles as a Theranostic Agent for Near‐Infrared Fluorescence Imaging and Thrombolysis of Blood Clots

“…A schematic representation of the fabrication of tPA‐conjugated NETs is shown in Figure 1 . It depicts the insertion of the lipid linker molecule, 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐polyethylene glycol‐aldehyde group (DSPE‐PEG‐CHO) into the membrane of EGs followed by mechanical extrusion to obtain nanosized EGs . These nanosized EGs were subsequently loaded with NIR imaging agent, ICG, in a hypotonic solution and then conjugated with tPA via amine‐aldehyde chemistry to create a theranostic nanoplatform with imaging and therapeutic capabilities.…”

“…Apart from liposomes, [4] synthetic polymers, [5] and magnetic nanoparticles, [8] attention has also been given to the use of biological materials such as erythrocytes as carriers for the delivery of therapeutic payloads to target sites. [9][10][11][12] One feature of normal erythrocytes is their naturally long circulation time (≈90-120 d), attributed to the presence of "self-marker" proteins on their surface. [13] Owing to this feature, constructs derived from erythrocytes may offer a promising approach for increased circulation time of their payload within the vasculature.…”

Cell membrane-derived nanomaterials for biomedical applications

“…In addition to their cancer drug delivery roots, nanoerythrosomes can be used for the delivery of photoactivatable agents for imaging and photothermal therapy [142], antihypertensive drugs [143], and perfluorocarbons for acoustic responsiveness [144]. Nanoerythrosomes have also been bestowed additional targeting functionality via the conjugation of antibodies to a polymeric tether [145]. Beyond RBCs, stem cells are a popular source of membrane material due to their tumor targeting ability.…”