Red Blood Cell Membrane Bioengineered Zr-89 Labelled Hollow Mesoporous Silica Nanosphere for Overcoming Phagocytosis

Abstract

Biomimetic nanoparticles (NPs) have been actively studied for their biological compatibility due to its distinguished abilities viz. long-term circulation, low toxicity, ease for surface modification, and its ability to avoid phagocytosis of NPs by macrophages. Coating the NPs with a variety of cell membranes bearing the immune control proteins increases drug efficacy while complementing the intrinsic advantages of the NPs. In this study, efforts were made to introduce oxophilic radiometal 89 Zr with hollow mesoporous silica nanospheres (HMSNs) having abundant silanol groups and were bioengineered with red blood cell membrane (Rm) having cluster of differentiation 47 (CD47) protein to evaluate its long-term in vivo behavior. We were successful in demonstrating the increased in vivo stability of synthesized Rm-camouflaged, 89 Zr-labelled HMSNs with the markedly reduced 89 Zr release. Rm camouflaged 89 Zr-HMSNs effectively accumulated in the tumor by avoiding phagocytosis of macrophages. In addition, re-injecting the Rm isolated using the blood of the same animal helped to overcome the immune barrier. This novel strategy can be applied extensively to identify the long-term in vivo behavior of nano-drugs while enhancing their biocompatibility.

Cell-mediated and cell membrane-coated nanoparticles for drug delivery and cancer therapy

“…CD47 lacking RBCs were rapidly cleared from the bloodstream by splenic red pulp macrophages. CD47 receptor presence on RBCs prevented this elimination by binding to the inhibitory SIRPα where it induces phosphorylation, leading to the activation of protein phosphatase, which in turn inhibits the phagocytic synapses and eventually blocks phagocytosis [ 117 ] . Macrophages may use several nonspecific activating receptors and rely on the presence or absence of CD47 to distinguish themselves from foreign substances.…”

“…Using the CD47 receptor to functionalize the NPs via cell membrane engineering or surface coating can help in longer circulation time and eventually better therapeutic outcomes in nanomedicine approaches. CD47 expressing cell membranes such as RBCs are co-extruded/coated along with other cell membranes to prepare cell membrane-coated NPs, which can avoid phagocytic elimination by macrophages and increase circulation time for prolonged drug release [ 117 ] .…”

Biosafety of mesoporous silica nanoparticles: a combined experimental and literature study

“…administration. MS particles were accumulated mostly in liver and spleen, fairly in lung, and slightly in other organs [34,40,42,44,[48][49][50][51][52][53][54][55][56]. In liver, spleen and lung, the MS particles were accumulated within 5-30 min after i.v.…”

Guest Edited Collection: Radioisotopes and radiochemistry in health science

“…Radiometals have their deserved place in the toolbox of nuclear medicine: cobalt ( 57 Co, 271.8 d; as a surrogate for 55 Co, 17.5 h) and indium ( 111 In, 2.8 d) were used as labels for affibody monomers targeting tumours in BxPC-3 xenografted mice 27 . A further contribution broaches the application of nanospheres labelled with 89 Zr (78.4 h) 28 , a positron emitter with a half-life roughly matching the in vivo circulation of antibodies.…”