Abstract

The unique structural features and stealth properties of a recently developed red blood cell membrane-cloaked nanoparticle (RBC-NP) platform raise curiosity over the interfacial interactions between natural cellular membranes and polymeric nanoparticle substrates. Herein, several interfacial aspects of the RBC-NPs are examined, including completeness of membrane coverage, membrane sidedness upon coating, and the effects of polymeric particles' surface charge and surface curvature on the membrane cloaking process. The study shows that RBC membranes completely cover negatively charged polymeric nanoparticles in a right-side-out manner and enhance the particles' colloidal stability. The membrane cloaking process is applicable to particle substrates with a diameter ranging from 65 to 340 nm. Additionally, the study reveals that both surface glycans on RBC membranes and the substrate properties play a significant role in driving and directing the membrane-particle assembly. These findings further the understanding of the dynamics between cellular membranes and nanoscale substrates and provide valuable information toward future development and characterization of cellular membrane-cloaked nanodevices.

Highlights

  • While the development of RBC-inspired drug carriers has focused primarily on mechano-mimicry[11,12,13] and protein functionalization,[5] the present study introduces a different emphasis on surface glycans, which represent the predominant moieties on cellular surfaces.[14]

  • The membranes were bath sonicated for 3 min using an FS30D bath sonicator (Fisher Scienti c, Waltham, MA) at a frequency of 42 kHz and a power of 100 W and subsequently extruded through a 100 nm polycarbonate porous membrane using an Avanti mini extruder to form RBC membrane vesicles

  • red blood cell membranecloaked nanoparticle (RBC-NP) present a unique nanocarrier platform that combines the immunomodulatory properties of natural cellular components with the cargo carrying capacity of polymeric nanoparticles

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Summary

Introduction

Recent advancement in biology and materials engineering has led to surging interest in bio-inspired nanodevices with biomimetic functionalities.[1,2,3] Exploiting the immunomodulatory self-marker proteins commonly found in cells for nanocarrier functionalization has bestowed unique anti-phagocytic properties and prolonged in vivo survival onto nanoparticles.[4,5] Among bio-inspired nanocarriers, a recently developed RBC membrane-cloaked nanoparticle (RBC-NP) platform presents an intriguing system as it utilizes the RBC membrane content in its entirety for immune-evasive stealth camou age[6,7] and therapeutic purposes.[8,9] Upon unilamellar membrane coating, RBC-NPs display self-marker proteins with a right-side-out orientation bias,[10] which contributes to the prolonged in vivo circulation time of the platform. The unique structural features and properties of RBC-NPs raise curiosity concerning the biomembrane–particle interface that plays a signi cant role in enabling colloidal stability and preserving biomimetic functionalities of the platform. We dissect the RBC-NP system to shed light on the mechanisms that elegantly bridge synthetic polymeric particles with natural cellular membranes

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