Site-selective antibody-lipid conjugates for surface functionalization of red blood cells and targeted drug delivery

Biquan Li, Dingdong Yuan, Hongfei Chen, Xun Wang, Yujie Liang, Clarence T.T. Wong, Jiang Xia

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

Displaying antibodies on carrier surfaces facilitates precise targeting and delivery of drugs to diseased cells. Here, we report the synthesis of antibody-lipid conjugates (ALCs) through site-selective acetylation of Lys 248 in human Immunoglobulin G (IgG) and the development of antibody-functionalized red blood cells (immunoRBC) for targeted drug delivery. ImmunoRBC with the HER2-selective antibody trastuzumab displayed on the surface (called Tras-RBC) was constructed following a three-step procedure. First, a peptide-guided, proximity-induced reaction transferred an azidoacetyl group to the ε-amino group of Lys 248 in the Fc domain. Second, the azide-modified IgG was subsequently conjugated with dibenzocyclooctyne (DBCO)-functionalized lipids via strain-promoted azide–alkyne cycloaddition (SPAAC) to result in ALCs. Third, the lipid portion of ALCs was then inserted into the cell membranes, and IgGs were displayed on red blood cells (RBCs) to construct immunoRBCs. We then loaded Tras-RBC with a photosensitizer (PS), Zinc phthalocyanine (ZnPc), to selectively target HER2-overexpressing cells, release ZnPc into cancer cells following photolysis, and induce photodynamic cytotoxicity in the cancer cells. This work showcases assembling immunoRBCs following site-selective lipid conjugation on therapeutic antibodies and the targeted introduction of PS into cancer cells. This method could apply to the surface functionalization of other membrane-bound vesicles or lipid nanoparticles for antibody-directed drug delivery.

Original languageEnglish
Pages (from-to)302-309
Number of pages8
JournalJournal of Controlled Release
Volume370
DOIs
Publication statusPublished - Jun 2024

Keywords

  • Antibody-lipid conjugates
  • ImmunoRBC
  • Photosensitizer
  • Site-selective antibody reaction
  • Targeted photodynamic therapy

ASJC Scopus subject areas

  • Pharmaceutical Science

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