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  • Title: CD123/CD33 dual-antibody modified liposomes effectively target acute myeloid leukemia cells and reduce antigen-negative escape.
    Author: Sun S, Zou H, Li L, Liu Q, Ding N, Zeng L, Li H, Mao S.
    Journal: Int J Pharm; 2019 Sep 10; 568():118518. PubMed ID: 31319147.
    Abstract:
    Most antibody-based therapies for AML target a single antigen on the surface of AML cells, which has a limited clinical benefit due to unsatisfied targeting ability and antigen-negative escape. Here we described the development and specific targeting of daunorubicin (DNR)-loaded CD123/CD33 dual-antibody modified liposome, CD123/CD33-LP-DNR. Since the majority of AML cells carries at least one of the antigens of CD123 and CD33, it is promising to treat AML using the dual-targeting agents. In this study, antibody mixture of CD123 and CD33 (1:1, molar ratio) were thiolated and coupled to Mal-PEG2000-DSPE, then the antibody-Mal-PEG2000-DSPE conjugations were inserted on the DNR-loaded PEGylated liposomes (PEG-LP-DNR) via a post insertion method to prepare CD123/CD33-LP-DNR (antibody/S100PC, molar ratio, 0.06%). The cellular uptake and cytotoxicity were evaluated in THP-1 (CD123brightCD33bright) and HL-60 (CD123dimCD33bright) cells. Compared to the unmodified liposome, CD123/CD33-LP-DNR showed higher cellular uptake which was 1.8-times and 1.6-times in both THP-1 and HL-60 cells, respectively, while the cellular uptake increased to 1.5-times only in the CD123bright cells for the single-antibody modified liposome, CD123-LP-DNR. MTT assay indicated stronger cytotoxicity of CD123/CD33-LP-DNR than CD123-LP-DNR on AML cells. The results indicated that CD123/CD33-LP-DNR might present an effective delivery strategy to enhance the targeting ability against AML cells and potentially reduce the antigen-negative escape.
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