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RBC Membrane-Camouflaged Nanoparticle Development

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At CD Formulation, we have developed methods to cloak nanoparticles with red blood cell (RBC) membranes, exploiting these cells' abilities to efficiently carry nucleic acid therapeutics. Through advanced formulation strategies, we engineer stealth nanoparticles that evade immune detection like natural RBCs. As a leader in biomimetic nanoparticle design, we aim to provide innovative solutions that strengthen our partners' progress in developing novel genetic and cellular medicines.

What is RBC Membrane-Camouflaged Nanoparticle?

An innovative type of nanocarrier, RBC membrane camouflage nanoparticles, is being developed for targeted drug delivery. A "stealth nanoparticle" is designed to evade phagocytic clearance and mimic the natural circulating behavior of erythrocytes by encapsulating pharmaceutical payloads within lipid-polymer nanoparticles and decorating their exterior with outer membranes harvested from erythrocytes. This allows them to potentially circulate for prolonged periods while retaining the ability to transport or release their cargo to desired tissues or cell types.

RVs fused with polymer nanoparticlesRVs fused with polymer nanoparticles (Xia Q.; et al. 2019)

How Do We Develop RBC Membrane-Camouflaged Nanoparticles?

  • Preparation of RVs

Process of RBC vesicles preparation - CD Formulation

  • Whole blood was collected, and plasma and RBCs were separated by centrifugation.
  • The isolated RBCs are lysed using a hypotonic buffer to release the intracellular contents while keeping the membranes intact.
  • Mechanical forces like extrusion or sonication are applied to shear the RBC membranes into smaller vesicles (RVs) of defined size.
  • We thoroughly wash the vesicle solution using ultracentrifugation to remove cell debris and lysate components from the membrane preparation.
  • The RVs are checked for shape, size distribution, protein and lipid composition using techniques such as fluorescence microscopy, TEM and DLS.
  • Development of Nanoparticles Loaded with Nucleic Acid

Polymeric nanoparticles: We formulate biodegradable/biocompatible polymers like PLGA, PLA, PEG into nanoparticles using emulsion/solvent diffusion techniques.
Lipid nanoparticles: Cationic/neutral lipids and helper lipids are formulated to create lipid nanoparticles.
Surface modifications: Particles may be PEGylated or targeted for improved biodistribution and fusion to erythrocyte membranes.

  • Vesicle-Particle Fusion

Vesicles are decorated onto the nanoparticle surface using gentle extrusion/sonication and membrane fusion is promoted via electrostatic/hydrophobic interactions.

Conjugates are purified through centrifugation washing to remove any unattached vesicles.

We can test the storage stability of membrane-camouflaged nanoparticles under different conditions.

Cellular uptake, internalization pathways, transfection efficiency and expression profiles are examined in relevant cell models.

How Do We Characterize RBC Membrane-Camouflaged Nanoparticles?

  • DLS analysis of physical and chemical parameters such as size, polydispersity, and zeta potential.
  • TEM/SEM for morphology analysis.
  • SDS-PAGE and Western Blotting for membrane protein analysis.
  • Flow cytometry for membrane marker expression.
  • Confocal microscopy for cellular uptake studies.
  • Fluorescence colocalization for nanoparticle core-shell structure analysis.

Advantages of Our RBC Membrane-Camouflaged Nanoparticle Development Services

  • We develop RBC membrane-camouflaged nanoparticles as versatile platforms that can accommodate various types of nucleic acids (e.g., mRNA, siRNA, or plasmid DNA) and facilitate different applications in gene therapy and biomedical research.
  • The erythrocyte membrane coating preserves natural proteins and receptors, which can contribute to improved targeting and cellular interactions.
  • Our development services offer customization and optimization options, tailoring the nanoparticles' size, surface charge, and membrane composition to suit specific applications and enhance delivery efficiency.
  • Biocompatibility, immune suppression, and safety are enhanced when nanoparticles are coated with erythrocyte membranes.

By leveraging cell membrane coating technologies, CD Formulation creates erythrocyte membrane camouflaged nanoparticles that deliver nucleic acid therapeutics safely and effectively. Contact us to explore how our RBC membrane-camouflaged nanoparticle development services can advance your research!

References

  1. Xia Q.; et al. Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application. Acta Pharm Sin B. 2019, 9(4):675-689.
  2. Hu C.M.; et al. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc Natl Acad Sci U S A. 2011, 108(27):10980-5.
  3. Vincy A.; et al. Recent progress in red blood cells-derived particles as novel bioinspired drug delivery systems: challenges and strategies for clinical translation. Front Chem. 2022, 10:905256.
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